Serum Aspartate Aminotransferase Activities Research Articles

The Protective Effects of Water Extracts of Compound Turmeric Recipe on Acute Alcoholism: An Experimental Research Using a Mouse Model.

Acute alcoholism (AAI) is a common emergency. Currently, there is a lack of preventive and therapeutic drugs with superior safety and efficacy. Curcuma longa, Panax ginseng, Pueraria lobata, Pueraria flower, and Hovenia dulcis Thunb., which are the components of compound turmeric recipe (CTR), are, respectively, used in China as adjuvant therapeutic agents for AAI and alcoholic liver injury, respectively. The purpose of this research was to investigate the effect of traditional compound turmeric recipe in anti-inebriation treatment and to identify its underlying mechanisms. The mice were administered with CTR mixture, and ethanol was subsequently given to mice by gavage. The effects of CTR on the righting reflex, 24-hour survival, drunken behavior, blood ethanol concentration, and pathological changes of liver are depicted. The activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were detected. Besides, the activities of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), cytochrome P450 (P450), superoxide dismutase (SOD), and malondialdehyde (MDA) in the liver and the levels of β-endorphin (β-EP) and leucine enkephalin (LENK) in the brain were also measured. Our results demonstrated that CTR can increase the activities of ADH, ALDH, P450, and SOD and decrease the contents of TNF-α, IL-8, and MDA in the liver. In addition, it can decrease the activities of ALT, AST, and ALP in serum and β-EP and LENK activities in the brain. CTR showed effects on prevention of acute alcoholism, promoting wakefulness, and alleviating alcoholic liver injury, which were likely mediated by the above mechanisms.

Impacts of Titanium Dioxide Nanoparticles on Serum Parameters and Enzyme Activities of Clarias gariepinus.

Impacts of titanium dioxide nanoparticles (TiO2 NPs) on serum glucose, albumin, total protein, cholesterol, triglyceride, sodium (Na+), potassium (K+), and chloride ion (Cl-) levels and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and cholinesterase (ChE) activities of Clarias gariepinus were determined after exposing the fish to 1, 5 and 10mg/L titanium applied as TiO2 over 1, 4 and 7days. No mortality was observed during the experiments. Serum glucose and albumin levels increased while serum total protein, cholesterol and triglyceride levels decreased compared to control at the end of the 7th day. Serum Na+, K+ and Cl- levels of C. gariepinus decreased after 7days of exposure to 10mg/L TiO2 NPs. ChE activity decreased and AST, ALT, ALP activities increased at all exposure concentrations and LDH activities increased compared to control after 4 and 7days of exposure to TiO2 NPs in C. gariepinus.

Elobixibat, an ileal bile acid transporter inhibitor, ameliorates non-alcoholic steatohepatitis in mice.

Recent studies have suggested that several types of toxic bile acids (BAs) are involved in the pathogenesis of non-alcoholic steatohepatitis (NASH). In the present study, we aimed to determine whether elobixibat, an ileal bile acid transporter (IBAT) inhibitor, would ameliorate NASH in mice. C57BL/6N mice were fed a methionine and choline-deficient (MCD) to induce NASH or standard diet as control for 8weeks (n = 5 per group). The MCD diet-fed mice were administered elobixibat 5days a week for 4weeks by gavage (n = 5). The effects of the treatments on liver histopathology, proinflammatory cytokine concentrations, intestinal epithelial tight junctions, and the intestinal microbial composition were then assessed. In MCD-fed mice, hepatic fibrosis and inflammatory cell infiltration developed, and the serum aspartate transaminase activity and BA concentration were higher than the control. In addition, the proinflammatory cytokine concentrations were high in the liver and mesenteric lymph nodes (MLN), and the expression of intestinal epithelium tight junction proteins, claudin1, was increased. In the intestinal microbial composition, the abundance of the Lachnospiraceae and Ruminococcaeae were decreased, whereas that of the Enterobacteriaceae was increased. Treatment with elobixibat reduced the serum BA and increased the fecal BA concentration, and ameliorated the liver inflammation and fibrosis. It also reduced the expression of proinflammatory cytokines in the liver and MLNs, and transforming growth factor-β expression in the liver. Finally, elobixibat normalized intestinal tight junction protein level and the composition of the intestinal microbiota. Elobixibat ameliorates NASH-related histopathology, reduces cytokine expression, and normalizes the intestinal microbial composition in MCD-fed mice, which suggests that it may represent a promising candidate for the therapy of NASH.

Lemon Balm and Dandelion Leaf Extracts Synergistically Protect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.

Dietary Beta-Hydroxy Beta-Methyl Butyrate Supplementation Alleviates Liver Injury in Lipopolysaccharide-Challenged Piglets.

The current study was performed to investigate whether dietary β-hydroxy-β-methylbutyrate (HMB) could regulate liver injury in a lipopolysaccharide- (LPS-) challenged piglet model and to determine the mechanisms involved. Thirty piglets (21 ± 2 days old, 5.86 ± 0.18 kg body weight) were randomly divided into the control (a basal diet, saline injection), LPS (a basal diet), or LPS+HMB (a basal diet + 0.60% HMB-Ca) group. After 15 d of treatment with LPS and/or HMB, blood and liver samples were obtained. The results showed that in LPS-injected piglets, HMB supplementation ameliorated liver histomorphological abnormalities induced by LPS challenge. Compared to the control group, the activities of serum aspartate aminotransferase and alkaline phosphatase were increased in the LPS-injected piglets (P < 0.05). The LPS challenge also downregulated the mRNA expression of L-PFK, ACO, L-CPT-1, ICDH β, and AMPKα1/2 and upregulated the mRNA expression of PCNA, caspase 3, TNF-α, TLR4, MyD88, NOD1, and NF-κB p65 (P < 0.05). However, these adverse effects of the LPS challenge were reversed by HMB supplementation (P < 0.05). These results indicate that HMB may exert protective effects against LPS-induced liver injury, and the underlying mechanisms might involve the improvement of hepatic energy metabolism via regulating AMPK signaling pathway and the reduction of liver inflammation via modulating TLR4 and NOD signaling pathways.

Aspartate aminotransferase and cardiovascular disease—a narrative review

: This narrative review summarized the existing knowledge on the association between aspartate aminotransferase (AST) and cardiovascular disease (CVD). AST plays a key role in the metabolism of amino acids, maintenance of NAD+/NADH ratio in cells, Krebs cycle activity, synthesis of purine/pyrimidine bases, urea and protein synthesis and gluconeogenesis. In humans, AST exists as two genetically and immunologically distinct isoenzymes: cytoplasmic AST and mitochondrial AST and both forms are found in circulation. AST activity is widely distributed across human tissues with the highest activity found in heart, liver, skeletal muscle, kidney and brain. An elevated AST activity may reflect tissue damage (plasma membrane disruption or apoptosis), plasma membrane bleb formation, increased tissue expression and macroenzymes (complexes of AST with plasma proteins). Serum AST activity is increased in patients with acute myocardial infarction in proportion with the extent of myocardial necrosis. Epidemiological evidence suggests the existence of an association between AST activity and CVD or mortality with positive, inverse or U (or J)-shaped association patterns. An elevated AST level not occurring in the setting of inflammatory liver disease may signify an increased cardiovascular risk related to nonalcoholic fatty liver disease (NAFLD), cardiometabolic risk factors (metabolic syndrome, abdominal obesity, insulin resistance and diabetes), chronic alcoholism and structural heart disease (myocardial infarction or congestive heart failure). A positive association between AST and CVD is more common in epidemiological studies in Asian population. Low AST levels may reflect increased cardiovascular risk related to vitamin B6 deficiency, advanced chronic kidney or liver diseases and inflammatory diseases. High and low AST levels have clinical meaning and both of them should be analyzed.

Effect of AgpP-P phytase supplementation on productivity, nutrient availability, zoo-sanitary meat quality and serum biochemical parameters of broiler chickens

The objective of this study was to assess the effect of AgpP-P phytase supplementation on productivity, nutrient availability, zoo-sanitary assessment of meat and serum biochemical parameters of Hubbard broilers. A total of 180 one-day-old Hubbard broiler chickens were randomly divided into 2 groups (control and experimental) with 3 replicates and 30 broilers per replicate. In the experimental group, the diet was supplemented with phytase preparation at 1000 FTU/kg. Results showed that phytase supplementation increased body weight and absolute weight gain in Hubbard broilers, while reducing the total amount of feed consumed by birds (P < 0.05). Phytase improved the availability and absorption of organic nutrients, calcium and phosphorus. However, no differences were observed for N absorption (P<0.05). Phytase supplementation increased Ca and P contents, total protein level and alanine aminotransferase activity, and reduced urea level, aspartate aminotransferase and alkaline phosphatase activities in serum (P < 0.05). The meat of phytase-fed broilers meets Russian State Standards for fresh, good-quality meat based on organoleptic and physico-chemical characteristics. In conclusion, it was established that the addition of phytase at 1000 FTU/kg to the diet for broilers enhances the digestibility of the organic and mineral components of the feed ration, increases body weight in birds and reduces the amount of feed consumed.

Potential Ameliorative Effects of L-Carnitine on Imidacloprid-Induced Hepato- and Nephrotoxicity in Male Albino Rats

The current study was intended to evaluate the possible protective role of L-Carnitine (LC) against imidacloprid (IM)-induced hepato- and nephrotoxicity in male albino rats. Thirty male albino rats were divided into 6 groups (n=5); control group, IM (32 mg/kg BW, 1/10 LD50)-treated group, LC200 (200 mg/kg BW)-treated group, LC400 (400 mg/kg BW)-treated group, IM+LC200-treated group, and IM+LC400-treated group. All treatments were given by oral route once daily for four weeks. Hematologically, the results exhibited that IM administration induced a significant decrease in red blood cells (RBCs) count, hemoglobin (Hb) and hematocrit (Ht) values. The erythrocytic indices (MCV, MCH and MCHC) displayed non-significant change in all treated groups. However, IM-treated group showed a significant leukocytosis and thrombocytosis after four weeks of treatment as compared to control group. Biochemically, the results revealed that IM convinced a significant elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) activities, as well as serum total bilirubin (TB), direct bilirubin (DB) and indirect bilirubin (IB), globulins, urea, creatinine, potassium (K+), pro-inflammatory cytokines (tumor necrosis factor- alpha and interleukin-6) levels at the end of experiment matching with the control group. However, IM administration resulted in a significant diminution in the serum of total proteins (TP), albumin, and sodium (Na+) levels, with a significant increase and decrease respectively in the levels of lipid peroxidation and antioxidant biomarker in the hepatic and renal tissues of rats after four weeks of treatments as compared to control group. Histopathologically, IM administration revealed marked degenerative and necrotic alterations in the liver and kidney. Conversely, LC treatment at two doses (200 and 400 mg) ameliorated IM-induced alterations in the blood picture, oxidative damage and inflammation in the liver and kidneys.Finally, it could be concluded that treatment with LC at two doses (200 and 400 mg) ameliorated IM-induced oxidative damage, alterations in the hematology, liver and kidney function tests, as well as their histopathology. However, administration of LC at a dose of 400 mg/kg BW showed better protective effects against IM-induced hepato-nephrotoxicity as compared to the low dose (200 mg/kg BW).

Effect of Adrenergic Drugs on the Lipopolysaccharide-Induced Oxidative Stress and Liver Damage in the Rat

Aim: We aimed to investigate the effect of the adrenergic system on oxidative stress and liver damage during mild systemic inflammation in rats. Methods: For this purpose, Eschrechia coli lipopolysacchride (LPS; 300μg/kg) was intraperitoneally injected either alone or along with the α-2 adrenoceptor antagonist yohimbine, the non-selective β adrenoceptor antagonist propranolol, the and β-adrenoceptor agonist adrenaline and rats euthanized 4h later. The effects of these drugs in saline-treated rats were also studied. Serum alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase activities were measured. Liver tissue levels of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH) were determined and liver histology evaluated. Results: In saline-treated rats (i) yohimbine caused significantly increased ALT, AST and ALP in serum. In addition, yohimbine increased MDA, NO and decreased GSH in liver tissue and caused cytoplasmic vacuolations and cellular infiltration: (ii) adrenaline treatment increased serum ALT, AST, liver MDA, decreased liver GSH and caused minute vacuolar degeneration and foci of necrosis; (iii) in contrast, there were no biochemical or histologic alterations after propranolol treatment. In endotoxaemic rats; (i) serum aminotransferases and alkaline phosphatase were significantly increased by yohimbine together with increased liver MDA, NO and decreased GSH content; (ii) serum ALT decreased by propranolol and adrenaline while serum ALP increased by adrenaline; (iii) liver GSH increased by propranolol; (iv) LPS administration caused acute liver damage in the form of foci of necrosis, vacuolar degeneration and aggregates of inflammatory cellular infiltration. Compared with the LPS only group, treatment with yohimbine increased while propranolol or adrenaline produced less liver damage. Conclusions: Thus, blockade of α-2 adrenoceptors increased while β adrenoceptor antagonism decreased oxidative stress and liver damage following LPS administration in rats. Collectively, these results indicate a benefit from blockade of beta-adrenoceptors in protecting the liver during mild systemic inflammation in part by decreasing oxidative stress.

Hepatoprotective effects of ginsenoside Rk3 in acetaminophen-induced liver injury in mice by activation of autophagy.

Acetaminophen (APAP)-induced acute liver injury (AIALI) is one of the most common causes of acute liver failure. Owing to the limitations of N-acetylcysteine (NAC), which is the only antidote currently used in clinical practice for APAP, there is a need to develop new therapies that can provide extensive protection against AIALI. Ginsenoside Rk3 is a rare ginsenoside extracted from Panax notoginseng and a previous study has reported its excellent hepatoprotective function. In this study, we explored the therapeutic potential of ginsenoside Rk3 in APAP-induced acute liver injury. We found that ginsenoside Rk3 could reduce APAP-induced hepatotoxicity by reducing serum alanine aminotransferase and aspartate aminotransferase activity and pathological damage to the liver. Moreover, ginsenoside Rk3 could inhibit APAP-induced liver inflammation and oxidative stress by inhibiting the production of oxidative molecules, increasing the production of antioxidant molecules, and reducing the infiltration of inflammatory cells and the production of pro-inflammatory cytokines. Further mechanistic investigations revealed that the therapeutic effect of ginsenoside Rk3 was mainly dependent on the continuous activation of autophagy. Chloroquine, an autophagy inhibitor, was found to inhibit these protective effects. Therefore, ginsenoside Rk3 shows potential as a novel hepatoprotective agent to prevent drug-induced liver injury.

Ameliorating Effect of Green Tea Aqueous Extract against Histo pathophysiological Changes Induced by Ciprofibrate in the liver of Male Albino Rats

Background: The liver is a specific target for drug toxicity because of its role in removal and metabolism of chemicals by converting drugs into another forms that can be readily removed from the body. It is known that the main function of the liver is the elimination of toxins that may enter the body, thus becoming vulnerable damaged during this mechanism, which can be revealed as bleeding, congestion, necrosis or other conditions of liver injury. Ciprofibrate belongs to widely used class of lipid-regulating agents, which stimulate hepatic cells and the hepatic cell becomes uncontrollably divided, causing liver growth. It causes liver cell proliferation in addition to other pleiotropic effects such as peroxisome proliferation and induction of certain peroxisomal and cytosolic enzymes in liver. Objective: The present study aimed to evaluate the potential beneficial effects of green tea aqueous extract administration against the biochemical and histological alterations induced in the liver by ciprofibrate in male rats. Materials and Methods: In the current study 3 groups of 6 male rats were used (Control group, 100mg\Kg body weight, and Cipro 100mg\Kg body weight with green tea). The rats have been treated daily orally by gavages for 21 days. On the last day of the experiment the animals were killed then blood samples and parts from the liver were collected. Liver function was examined for the serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), alkaline phosphates (ALP), enzyme activities, and serum total &amp; direct bilirubin concentrations. The histopathological investigation was conducted for the liver tissues of all groups. Results: Treatment of male rats with 100 mg\Kg body weight of ciprofibrate caused a significant increase in serum ALT, AST, and ALP activities, total, and direct bilirubin concentration. Histologically, there were histological changes in central vein area and portal zones, revealed congestion in blood sinusoids, necrosis in hepatic cells, and damage in central vein lining epithelium. Co-administration of green tea aqueous extract with Ciprofibrate significantly improved the structural changes in the liver and the serum ALT, AST, and ALP activities, total, and direct bilirubin concentrations were significantly declined. Conclusion: It can be concluded that Ciprofibrate treatment induced elevation in liver function tests and severe histopathological changes and green tea aqueous extract was able to protect the liver against these effects in male rats. So, the patients should be advised to take green tea aqueous extract while they are treated by ciprofibrate.

Post-treatment with glycyrrhizin can attenuate hepatic mitochondrial damage induced by acetaminophen in mice.

Overdose of acetaminophen (APAP) is responsible for the most cases of acute liver failure worldwide. Hepatic mitochondrial damage mediated by neuronal nitric oxide synthase- (nNOS) induced liver protein tyrosine nitration plays a critical role in the pathophysiology of APAP hepatotoxicity. It has been reported that pre-treatment or co-treatment with glycyrrhizin can protect against hepatotoxicity through prevention of hepatocellular apoptosis. However, the majority of APAP-induced acute liver failure cases are people intentionally taking the drug to commit suicide. Any preventive treatment is of little value in practice. In addition, the hepatocellular damage induced by APAP is considered to be oncotic necrosis rather than apoptosis. In the present study, our aim is to investigate if glycyrrhizin can be used therapeutically and the underlying mechanisms of APAP hepatotoxicity protection. Hepatic damage was induced by 300 mg/kg APAP in balb/c mice, followed with administration of 40, 80, or 160 mg/kg glycyrrhizin 90 min later. Mice were euthanized and harvested at 6 h post-APAP. Compared with model controls, glycyrrhizin post-treatment attenuated hepatic mitochondrial and hepatocellular damages, as indicated by decreased serum glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities as well as ameliorated mitochondrial swollen, distortion, and hepatocellular necrosis. Notably, 80 mg/kg glycyrrhizin inhibited hepatic nNOS activity and its mRNA and protein expression levels by 16.9, 14.9, and 28.3%, respectively. These results were consistent with the decreased liver nitric oxide content and liver protein tyrosine nitration indicated by 3-nitrotyrosine staining. Moreover, glycyrrhizin did not affect the APAP metabolic activation, and the survival rate of ALF mice was increased by glycyrrhizin. The present study indicates that post-treatment with glycyrrhizin can dose-dependently attenuate hepatic mitochondrial damage and inhibit the up-regulation of hepatic nNOS induced by APAP. Glycyrrhizin shows promise as drug for the treatment of APAP hepatotoxicity.

Apple polyphenols modulates the antioxidant defense response and attenuates inflammatory response concurrent with hepatoprotective effect on grass carp (Ctenopharyngodon idellus) fed low fish meal diet

Polyphenols are well known for its benefits to improve the antioxidant capacity and inflammation response in human but their positive response and underlying mechanism is not yet well established in fish. Therefore, a 60-day feeding trial was conducted to explore the effects of apple polyphenols (AP) for improving the health of grass carp. Fish were fed with plant protein based diets supplemented with 0, 1, 5, and 10 g of AP per kg. Results of the study showed that highest (10 g/kg) supplementation of AP exhibited lower growth of fish compared to other groups. Dietary inclusion of AP exhibited hepatoprotective effects via decreasing the activities of serum alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transaminase (P < 0.05), and hypocholesterolemic effects. AP supplementation improved the antioxidant status in terms of high level of antioxidant parameters in serum and intestine tissue, followed by a reduction in malondialdehyde content (P < 0.05). Antioxidant capacity was improved by AP via activation of Nrf2, and over expression of catalase and copper/zinc superoxide dismutase (P < 0.05). Additionally, AP supplementation exerted an anti-inflammation effect through the inhibition of TLR4 signaling pathway, followed by a notable decrease in the transcription of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α (P < 0.05). Thereafter, an enhancement of intestinal barrier function was observed in AP1, AP5 and AP10 groups in terms of overexpression of junction proteins such as ZO1, ZO2, ZO3, and Occludin (P < 0.05). These results documented that AP exhibited beneficial impacts on the health of grass carp through improving antioxidant capacity, suppression of inflammatory responses, and enhancement of intestinal barrier function. Overall, optimal dose of AP for grass carp is 5 g/kg diet.

Evaluation of in vitro and in vivo potential of Bacillus subtilis MBTDCMFRI Ba37 as a candidate probiont in fish health management

Bacillus subtilis MBTDCMFRI Ba37 (B. subtilis Ba37), an antibacterial strain isolated from the tropical estuarine habitats of Cochin, was evaluated for in vitro and in vivo potential, and its application as a candidate probiont in fish health management. B. subtilis Ba37 was characterized using their morphological and biochemical properties. It exhibited exoenzymatic activities, tolerance to various physiological conditions and a wide spectrum of antibacterial activity against aquaculture pathogens such as Vibrio and Aeromonas. In co-culture assay, B. subtilis Ba37 inhibited Vibrio anguillarum O1 (V. anguillarum O1) even with the initial cell count of 104 CFUmL−1. Cytotoxicity assay performed using the cell free supernatant (CFS) of B. subtilis Ba37 revealed its non toxic nature. A twenty one days of feeding trial was conducted in juveniles of Etroplus suratensis (E.suratensis) by administrating B. subtilis Ba37 to evaluate its efficacy on growth, immune parameters and antioxidant enzyme activities. Overall the supplementation of B. subtilis Ba37 enhanced significantly (P < 0.05) the survival rate, weight gain, specific growth (SGR), feed conversion ratio (FCR), protein efficiency ratio (PER), and feed efficiency (FE) of the fed animals as compared with the control. The immune parameters and antioxidant activities such as total protein, alkaline phosphatase (ALP), superoxide dismutase (SOD) and catalase were also improved significantly (P < 0.05) while serum alanine aminotransferase (SGOT) and serum aspartate aminotransferase (SGPT) activities were decreased slightly than the control. After fifteen days of challenge test, the fish fed with B. subtilis Ba37 showed higher relative percentage survival (RPS) than the control. Thus the study indicated the advantages of B. subtilis Ba37 to be used as a candidate probiont, which could be effectively utilized in managing diseases in aquaculture systems and to improve the health of the host.

Cardio-protective impact of gabapentin against doxorubicin-induced myocardial toxicity in rats; emphasis on modulation of inflammatory-apoptotic signaling

PurposeCardiotoxicity is one of the most commonly encountered adverse effects observed alongside the therapeutic use of doxorubicin (DOX), thus curbing its therapeutic utility. MethodsThe current study was conducted to evaluate the cardioprotective effect of gabapentin (Gaba), a Ca + 2 channel blocker with emerging pharmacological merits, against DOX-induced cardiotoxicity. Gaba was orally administered at two dose levels (10 and 30 mg/kg) for 21 days parallel to DOX injection. ResultsDOX induced significant functional, biochemical, and histopathological injury to the myocardium. Gaba treatment revealed a cardioprotective effect as manifested in the significant restoration of electrocardiogram parameters, including the heart rate, ST segment elevation, QRS and T wave amplitudes, and QT and PR intervals. The biomarkers of myocardial injury, namely serum creatine kinase, aspartate aminotransferase, and lactate dehydrogenase activities, significantly declined as well as the concomitant improvement of the myocardial oxidative status. Mechanistically, Gaba treatment significantly reduced the myocardial contents of c-Jun N-terminal kinase (JNK), the major modulator of inflammatory/apoptotic signaling. However, the myocardial contents of the apoptotic biomarkers caspase-8 and TRAIL also significantly declined. In isolated cardiomyocytes, Gaba treatment maintained the morphological characteristics of the cardiomyocytes and preserved their spontaneous beating characteristics. Nevertheless, the protein expression of caspase-8, JNK 1/2, and CD95L significantly declined with Gaba treatment. ConclusionGaba confers cardioprotective effects against DOX-induced myocardial injury and cardiotoxicity by modulating the inflammatory/apoptotic signaling pathway.

Hypoxia-induced miR-92a regulates p53 signaling pathway and apoptosis by targeting calcium-sensing receptor in genetically improved farmed tilapia (Oreochromis niloticus).

miR-92a miRNAs are immune molecules that regulate apoptosis (programmed cell death) during the immune response. Apoptosis helps to maintain the dynamic balance in tissues of fish under hypoxia stress. The aim of this study was to explore the role and potential mechanisms of miR-92a in the liver of tilapia under hypoxia stress. We first confirmed that CaSR (encoding a calcium-sensing receptor) is a target gene of miR-92a in genetically improved farmed tilapia (GIFT) using luciferase reporter gene assays. In GIFT under hypoxia stress, miR-92a was up-regulated and CaSR was down-regulated in a time-dependent manner. Knocked-down CaSR expression led to inhibited expression of p53, TP53INP1, and caspase-3/8, reduced the proportion of apoptotic hepatocytes, and decreased the activity of calcium ions induced by hypoxia in hepatocytes. GIFT injected in the tail vein with an miR-92a agomir showed up-regulation of miR-92a and down-regulation of CaSR, p53, TP53INP1, and caspase-3/8 genes in the liver, resulting in lower serum aspartate aminotransferase and alanine aminotransferase activities under hypoxia stress. These findings suggest that stimulation of miR-92a interferes with hypoxia-induced apoptosis in hepatocytes of GIFT by targeting CaSR, thereby alleviating liver damage. These results provide new insights into the adaptation mechanisms of GIFT to hypoxia stress.

Eubiotic effect of a dietary potassium diformate (KDF) and probiotic (Lactobacillus acidophilus) on growth, hemato-biochemical indices, antioxidant status and intestinal functional topography of cultured Nile tilapia Oreochromis niloticus fed diet free fishmeal

An 84 days experimental trial was undertaken to examine the influence of potassium diformate (KDF) and Lactobacillus acidophilus and their interaction on growth, biochemical of blood parameters, enzymes of antioxidant response and intestinal topography of Nile tilapia, Oreochromis niloticus, fingerlings fed fishmeal free diets. Six functional diets were formulated to contain two levels of L. acidophilus (0, 1.47 × 107 CFU kg−1), with each level being supplemented with 0, 5 g and 10 g KDF kg−1 diet, respectively. Fingerlings O. niloticus (n = 540; initial weight 4.29 ± 0.06 g) were randomly allocated into six groups (30 fish group−1 in triplicates). The results showed that the best values of growth, feed efficiency and biological parameters were recorded by fish fed diets containing 1.47 × 107 L. acidophilus CFU kg−1 and 10 g kg−1 KDF. Lower pH values in stomach and gut were noted in fish fed diet supplemented with 1.47 × 107 L. acidophilus CFU kg−1 and 10 g kg−1 KDF. Diets supplemented with L. acidophilus, KDF or in combination improved the hemoglobin, red blood cells and white blood cells count with insignificant differences among groups. The activities of serum alanine and aspartate aminotransferase decreased significantly (P < 0.05) by the addition of L. acidophilus and KDF in fish diets. Furthermore, addition of KDF and L. acidophilus significantly (P < 0.05) improved the serum total protein and albumin, but globulin not affected. The lowest value of uric acid was recorded in fish fed 5 g kg−1 KDF without addition of L. acidophilus, while there were no significant (P > 0.05) differences in creatinine content were found among treatments. Diets supplemented with L. acidophilus and/or KDF significantly (P < 0.05) improved phosphorus and calcium content. However, the activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and catalase (CAT) were highest in fish fed diet contained either 5 g or 10 g kg−1 KDF and 1.47 × 107 L. acidophilus CFU kg−1 (D4 and D6). Villi length and width in the middle intestine and number of goblet cell were shown to be promoted in fish fed diets 10 g KDF kg−1 or 10 g kg−1 KDF and 1.47 × 107 L. acidophilus CFU kg−1diet. In conclusion, the administration of a mixture of a probiotic and KDF is beneficial, as it effectively improves the gut morphology and the total antioxidant enzyme activity resulting in an overall enhancement of the fish growth performance.

Chlorella vulgaris ameliorates sodium nitrite-induced hepatotoxicity in rats.

The current was conducted to evaluate the ameliorating effect of Chlorella vulgaris (CV) extract against sodium nitrite-induced hepatotoxicity in rats. Forty-five rats were allocated randomly into 5 groups (n = 9). Group I (GI), control group: orally gavaged with normal saline daily. Group II (GII): orally gavaged with CV extract (70 mg/kg BW) for 3 months. Group III (GIII): orally gavaged with sodium nitrite (80 mg/kg BW) for 3 months. Group IV (GIV): received sodium nitrite as GIII and CV extract as GII simultaneously for 3 months. Group V (GV): received CV extract as GII and then, sodium nitrite as in GIII from the end of first month until the end of the experiment. Sodium nitrite significantly increased the activities of serum alanine aminotransferase, aspartate aminotransferase, and serum concentrations of tumor interleukin 1-β and necrosis factor α. In addition, it increased concentrations of malondialdehyde and nitric oxide and expression level of caspase-3 in the hepatic tissue. However, it decreased activities of hepatic glutathione peroxidase, catalase, and superoxide dismutase and induced degenerative and necrotic changes in hepatic tissues. In contrast, CV extract administration modulated sodium nitrite-induced inflammation, oxidative stress, and alteration in hepatic tissue function and architecture. This study indicated that CV extract modulated sodium nitrite-induced hepatic toxicity through decreasing oxidative stress and inflammation and enhancing antioxidant enzyme activities in hepatic tissue of rats.

Evaluation of berberine efficacy in reducing the effects of aflatoxin B1 and ochratoxin A added to male broiler rations

Many types of mycotoxins are found in food sources contaminated with fungi, and if these are ingested in large quantities or over a long period, they can affect the health of humans and domestic animals. Berberine (BBR) is a plant alkaloid with multiple pharmacological functions. This study aimed to investigate the effect of different levels of the plant alkaloid BBR on reducing toxic effects of aflatoxin B1 (AFB) and ochratoxin A (OTA) in broilers by examining performance characteristics, blood biochemistry, antioxidant systems, ileum morphology, and histopathology of the liver. The experiment was performed with 288 Ross 308 broilers reared in floor pens for 42 d in a randomized design with 9 treatments. Each treatment was replicated 4 times, and each replicate contained 8 chicks. Experimental treatments included (1) negative control diet with no additives (NC); (2) NC + 2 ppm AFB (positive control AFB; PCAFB); (3) NC + 2 ppm OTA (positive control OTA; PCOTA); (4) PCAFB + 200 mg/kg BBR; (5) PCAFB + 400 mg/kg BBR; (6) PCAFB + 600 mg/kg BBR; (7) PCOTA + 200 mg/kg BBR; (8) PCOTA + 400 mg/kg BBR; and (9) PCOTA + 600 mg/kg BBR. Compared with NC, feeding PCAFB and PCOTA diets reduced average daily feed intake, weight gain, serum concentrations of superoxide dismutase, glutathione peroxidase, and the length and width of ileum villi (P < 0.05). At the same time, these parameters increased in birds fed PCAFB or PCOTA diets supplemented with 600 mg/kg of BBR (P < 0.05). Feeding PCAFB and PCOTA diets increased feed conversion ratio (FCR), serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) activities, serum urea, and liver lesions compared with NC. By contrast, compared with PCAFB and PCOTA, adding 600 mg/kg BBR decreased FCR, AST, LDH, ALT, and GGT activities, urea, and liver lesions (P < 0.05). Overall, supplementation with 600 mg/kg BBR may improve growth performance, liver function, and antioxidant status of broilers fed diets contaminated with AFB and OTA.

STUDY OF IRRITANT AND SKIN-RESORPTIVE ACTION OF SODIUM-CONTAINING DRUG

Sodium-containing preparations have antimicrobial, anti-inflammatory and wound-healing activity, which determines their use in veterinary medicine. This effect is due to a wide range of physiological effects of sodium ions on animals metabolism. The article presents the results of experimental studies of the irritant effect of sodium-containing drugs: known – 2 % glycetinate, its analogues – 2 % ovocid, 3 % ovocid, 1.5 % potassium-sodium drug (Na / K, 1.5%). Studies of irritant and skin-resorptive action of drugs were performed by immersing the tail of animals in a test tube with the substance on white rats weighing 250–270 g. Four groups of rats were formed with 3 animals each: rats of I group (control) tails were immersed in test tubes with 2 % glycetinate, animals of II group – in test tubes with 2% oocide, III group – in test tubes with 3 % oocide, and in IV group rats – with Na / K, 1.5% drug. The exposure time was 4 hours. The animals were subjected to clinical observations, assessing their general condition and the reaction of the tail’s skin. The effect of drugs on the morphological and biochemical parameters of the rats blood was studied. The study of the local irritant effect of the studied drugs in rats from I, II and III groups showed a moderate local irritant reaction, as evidenced by the appearance of redness and thickening of the skin, and in group IV animals appeared only slight redness on the skin of the tails. This indicates a weaker local irritant effect of potassium-sodium-containing drug (1.5% K, Na), compared with other studied drugs.&#x0D; According to hematological studies, in the rats’s blood of groups III and IV, a reliable increase, within normal limits, the number of leukocytes and a decrease in hemoglobin content, compared with those of animals of group I. It was found that at 4 hours of the experiment under the action of the studied potassium-sodium drugs increases the permeability of Sodium and Potassium through the rats’s skin into the blood. In particular, in serum of animals from groups II and IV there was a reliable increase of Potassium content by 2.1 times, respectively, and a significant increase in Sodium content in the blood of animals from groups III and IV, compared with control group. In animals of groups II and IV there was a reliable increase of serum aspartate aminotransferase activity, and in rats of group III – increase of serum alanine aminotransferase, alkaline phosphatase activity and in triacylglycerol’s content, compared with rats of group I, which indicates the effect of 2 % glycecin analogues on metabolic processes in animals.