Histopathological Alterations In Liver Research Articles

Black radish root extract alleviates sodium valproate-induced liver damage via inhibiting mitochondrial membrane potential collapse and oxidative stress in mice

Objective: To explore the effect of black radish (Raphanus sativus L. var niger) root extract on liver enzymes, oxidative stress, and histopathological alterations in mice with sodium valproate-induced hepatotoxicity. Methods: Thirty-two mice were divided into four groups: the control group received drinking water by gavage, the second group was administered with 100 mg/kg of sodium valproate, the third group received 300 mg/kg of black radish root extract, and the fourth group was given both sodium valproate (100 mg/kg) and black radish root extract (300 mg/kg). After 28 days, the mice were euthanized, and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), along with liver malondialdehyde (MDA), reactive oxygen species (ROS), mitochondrial parameters, tumor necrosis factor-alpha (TNF-α) gene expression, and histopathological changes were assessed. Results: Sodium valproate caused hepatic damage in mice, characterized by elevated serum levels of liver enzymes, increased MDA and ROS levels and TNF-α gene expression, as well as histopathological alterations. The black radish root extract significantly alleviated sodium valproate-caused hepatic injury by decreasing the serum levels of ALT and AST, MDA, ROS, TNF-α gene expression, as well as mitochondrial impairment, but did not have a significant effect on sodium valproate-induced histopathological changes. Conclusions: The black radish root extract demonstrates protective effects against sodium valproate-induced liver injury, possibly through mitigating oxidative stress, mitochondrial impairment, and inflammatory mediator expression.

Impact of Mild Gestational Diabetes Mellitus on Maternal and Fetal Liver Histopathological Alterations

Background: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications that can affect the organ systems of the body in both the mother and fetus. This study aimed to determine the impact of mild GDM on maternal and fetal liver histopathological alterations. Materials and Methods: In this experimental study, 20 pregnant Wistar rats were randomly allocated in control and diabetic groups. Mild hyperglycemia was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on the 5th day of gestation. The control group received an equal volume of citrate buffer. The diabetic state was confirmed by a blood glucose level of 120–300 mg/dL. Maternal and fetal liver samples were obtained on day 19 of gestation and stained with hematoxylin and eosin for histopathological investigation. Results: Liver sections of diabetic dams exhibited edematous hepatocytes and scattered pyknotic and necrotic cells with dilated sinusoids and congested central veins. The portal tracts showed the proliferation of bile ducts with mild chronic inflammatory cells infiltrating together with fibrosis beyond the limited plate which extends to the central vein (porto-central fibrosis). Liver sections of their fetuses revealed edematous hepatocytes with increased necrotic cells, with pyknotic nuclei, dilatation of the hepatic sinusoids, and their central veins. There was also a relative increase in megakaryocytes, which promoted fibrosis and distorted vascular beds of the hepatic tissue. The portal tracts also showed bile duct proliferation. Conclusion: This study highlighted the adverse effects of uncontrolled mild GDM on liver structure in rat dams and their fetuses.

Toxicity and Hepatoprotective Effects of ZnO Nanoparticles on Normal and High-Fat Diet-Fed Rat Livers: Mechanism of Action.

This experiment aimed to evaluate the beneficial and toxic properties of synthetic zinc oxide nanoparticles (ZnO NPs) on the liver of normal and high-fat diet (HFD) fed-rats. The ZnO NPs were synthesized and, its characterizations were determined by different techniques. Effect of ZnO NP on cell viability, liver enzymes and lipid accumulation were measured in HepG2 cells after 24h. After that, rats orally received various dosages of ZnO NPs for period of 4weeks. Toxicity tests were done to determine the appropriate dose. In the subsequent step, the hepatoprotective effects of 5mg/kg ZnO NPs were determined in HFD-fed rats (experiment 2). The oxidative stress, NLRP3 inflammasome, inflammatory, and apoptosis pathways were measured. Additionally, the activity of caspase 3, nitric oxide levels, antioxidant capacity, and various biochemical factors were measured. Morphological changes in the rat livers were also evaluated by hematoxylin and eosin (H & E) and Masson trichrome. Liver apoptosis rate was also approved by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Treatment of animals with 5mg/ZnO NPs revealed potential hepatoprotective properties, while ZnO NPs at the doses of above 10mg/kg showed toxic effects. Antioxidant enzyme gene expression and activity were significantly augmented, while apoptosis, NLRP3 inflammasome, and inflammation pathways were significantly reduced by 5mg/kg ZnO NPs. Liver histopathological alterations were restored by 5mg/kg ZnO NPs in HFD. Our study highlights the hepatoprotective effects of ZnO NPs against the HFD-induced liver damage, involving antioxidant, anti-inflammatory, and anti-apoptotic pathways, indicating their promising therapeutic potential.

The Hepato and Reno Protective Role of Curcumin against the Alterations in Some Biochemical Parameter and Histological Damage Induced by Monosodium Glutamate in Male Albino Rats

The main objective of current research was to investigate toxicity effect of Monosodium glutamate and protective role of Curcumin on some blood biochemical parameters, body weight gain, relative organ weight and histopathological alterations in liver and kidney tissues in male albino rats. Twenty animals of male rats (Rattus norvegicus), their weight ranged from 111 to 165 gm. The animals were divided into four groups: Each animal group contained five rat, first group was control negative (-ve) administrated distilled water, the second group was control positive (+ve) administrated curcumin, third group was administrated by Monosodium glutamate (MSG) at dose 20 mg per one Kg and the forth group was administrated by Monosodium glutamate (MSG) at dose 20mg/Kg of body weight + curcumin at dose 100 mg per one Kg of body weight. All animal groups were administrated orally about 30 days. The study recorded significant p≥0.05 increment in liver and kidney function parameters included [Alanine transaminase (ALT), Aspartate aminotransferase (AST), Urea and creatinine] after oral administration of animals with MSG and MSG + Curcumin as a comparison with control groups. The study recorded significant decrement p≥0.05 in liver and kidney function parameters included ALT, AST, Urea and creatinine) in group was administrated MSG + Curcumin in comparison with group was administrated MSG only. Additionally, current study revealed histopathological changes in liver and kidney tissue in groups were administrated MSG and MSG+ curcumin compared with + curcumin compared with control groups. Furthermore, the study revealed that curcumin had protective effect and result in slight histopathological changes in liver and kidney tissue by reducing the damage and in group was treated by MSG+ curcumin for 30 days compared with MSG treated group.

Effects of sub-lethal concentrations of lindane on histo-morphometric and physio-biochemical parameters of Labeo rohita.

Lindane is a broad-spectrum insecticide widely used on fruits, vegetables, crops, livestock and on animal premises to control the insects and pests. The extensive use of pesticides and their residues in the soil and water typically join the food chain and thus accumulate in the body tissues of human and animals causing severe health effects. The study was designed to determine the toxicity effects of sub-lethal concentrations of lindane on hemato-biochemical profile and histo-pathological changes in Rohu (Labeo rohita). A significant increase in the absolute (p<0.05) and relative (p<0.05) weights was observed along with severe histo-pathological alterations in liver, kidneys, gills, heart and brain at 30μg/L and 45μg/L concentration of lindane. A significant (p<0.05) decrease in RBCs count, PCV and Hb concentration while a significant (p<0.05) increased leukocytes were observed by 30μg/L and 45μg/L concentrations of lindane at 45 and 60 days of the experiment. Serum total protein and albumin were significantly (p<0.05) decreased while hepatic and renal enzymes were significantly (p<0.05) increased due to 30μg/L and 45μg/L concentrations of lindane at days-45 and 60 of experiment compared to control group. The observations of thin blood smear indicated significantly increased number of erythrocytes having nuclear abnormalities in the fish exposed at 30μg/L and 45μg/L concentrations of lindane. ROS and TBARS were found to be significantly increased while CAT, SOD, POD and GSH were significantly decreased with an increase in the concentration and exposure time of lindane. The results showed that lindane causes oxidative stress and severe hematological, serum biochemical and histo-pathological alterations in the fish even at sub-lethal concentrations.

Biochemical and histopathological alterations of liver and kidney of Japanese quails due to lead toxicity and effects of vitamin C

Lead (Pb) is the most dangerous xenobiotic causing variety of negative impacts on human and animal health.The current study intended to investigate the effect of different doses of Pb on biochemical and histological abnormalities in the kidney and liver of quail and the beneficial effects of vitamin C. A total of 72 male quail, aged 12 days were allotted in four groups with four replications. Control group (T0) received normal diet, group T1 and T2 received Pb at a dose of 70 mg and 700 mg/kg body weight (bw) respectively for 21 days, while T3 had 700 mg Pb /kg bw for 10 days followed by only vitamin C supplementation at a dose of 70 mg/kg bw without any Pb for next 10 days. After end of treatment, blood serum was collected, and the kidney and liver were taken for a histoarchitecture study. Significant (p&lt;0.05) Pb-induced elevations of biochemical markers of liver and kidney were observed in different periods of treatment (except d21-period of T3) and decreased following vitamin C supplementation in d21 of T3 (except creatinine).The effect of Pb treatment included congestion, necrotic foci in different organs, reactive cells in central vein, degeneration of hepatocytes, necrosis in the portal area as well as renal tubular degeneration, all of which were slightly improved by vitamin C in group T3. So, the findings suggest that the use of vitamin C could be a potential preventative agent against Pb-induced toxicity.

Cylindrospermopsin exposure promotes redox unbalance and tissue damage in the liver of Poecilia reticulata, a neotropical fish species

ABSTRACT There is a growing concern regarding the adverse risks exposure to cylindrospermopsin (CYN) might exert on animals and humans. However, data regarding the toxicity of this cyanotoxin to neotropical fish species are scarce. Using the fish species Poecilia reticulata, the influence of CYN concentrations equal to and above the tolerable for drinking water may produce on liver was determined by assessing biomarkers of antioxidant defense mechanisms and correlated to qualitative and semiquantitative histopathological observations. Adult females were exposed to 0.0 (Control); 0.5, 1 and 1.5 μg/L pure CYN for 24 or 96 hr, in triplicate. Subsequently the livers were extracted for biochemical assays and histopathological evaluation. Catalase (CAT) activity was significantly increased only by 1.5 μg/L CYN-treatment, at both exposure times. Glutathione -S-transferase (GST) activity presented a biphasic response for both exposure times. It was markedly decreased after exposure by 0.5 μg/L CYN treatment but significantly elevated by 1.5 μg/L CYN treatment. All CYN treatments produced histopathological alterations, as evidenced by hepatocyte cords degeneration, steatosis, inflammatory infiltration, melanomacrophage centers, vessel congestion, and areas with necrosis. Further, an IORG >35 was achieved for all treatments, indicative of the presence of severe histological alterations in P. reticulata hepatic parenchyma and stroma. Taken together, data demonstrated evidence that CYN-induced hepatotoxicity in P. reticulata appears to be associated with an imbalance of antioxidant defense mechanisms accompanied by histopathological liver alterations. It is worthy to note that exposure to low environmentally-relevant CYN concentrations might constitute a significant risk to health of aquatic organisms.

Potential effects of spirulina and date palm pollens on zinc oxide nanoparticles -induced hepatoxicity, oxidative stress, and inflammation in male albino rats.

The application of Zinc oxide nanoparticles (ZnO NPs) is substantially growing in industrial products. Therefore, humans are increasingly exposed to ZnO NPs daily due to their extensive range of applications, raising worries about their possible toxicity. In this study, the ameliorative effects of raw Phoenix dactylifera L. (date palm) pollens (DPP) and Spirulina platensis (SP) independently against ZnO NPS-induced hepatoxicity in male albino rats were examined. Six groups (6/group) of adult male albino rats received oral treatment using distilled water (control), SP (1000 mg/kg b. wt.), DPP (100 mg/kg b. wt.), ZnO NPs (100 mg/kg b. wt.), ZnO NPs +SP, and ZnO NPs + DPP respectively for 15 days. The results of the biochemical investigation indicated that the administration of ZnO NPs substantially upregulated (p < 0.05) transaminases, alkaline phosphatase, and bilirubin serum levels. Malondialdehyde and pro-inflammatory cytokine serum levels were also elevated after ZnO NPs administration. Simultaneously, the downregulated catalase and glutathione peroxidase serum activities were significantly suppressed in ZnO NPs treated rats. Moreover, exposure to ZnO NPs induced liver histopathological alterations. The administration of SP and DPP ameliorated the aforementioned effects caused by ZnO NPs. This result can be attributable to the downregulation of hepatic transaminases, alkaline phosphatase, and bilirubin in the serum and the antioxidation system's equilibration, thus alleviating the accumulation of reactive oxygen species. SP and DPP are natural antioxidants with the potential to eliminate inflammation as well as oxidative damage caused by ZnO NPs in hepatic tissue.

Fuling-Zexie formula attenuates hyperuricemia-induced nephropathy and inhibits JAK2/STAT3 signaling and NLRP3 inflammasome activation in mice

Ethnopharmacological relevanceFuling-Zexie (FZ) formula, a traditional Chinese herbal prescription composed of Poria cocos (Schwan.) Wolf. (Poria), Pueraria lobate (Willd.) Howe. (Puerariae Lobatae Radix), Alisma orientale (Sam.) Julep. (Alismatis Rhizoma), and Atractylodes lancea (Thunb.) Dc. (Atractylodis Rhizoma), has been clinically used to ameliorate hyperuricemia (HUA) and its associated renal injury. Aim of studyThis study aims to explore the action and mechanism of FZ on renal inflammation and dysfunction caused by HUA. Materials and methodsFZ was orally administered to rapid HUA mouse induced by potassium oxonate (PO) and hypoxanthine (HX) for 7 days. Serum levels of uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), xanthine oxidase (XOD), adenosine deaminase (ADA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urine levels of UA, CRE and urinary albumin were determined by biochemical assays. Serum levels of interleukin (IL)-1β and IL-6 were tested by ELISA. Hematoxylin-eosin and Masson staining were used to examine kidney and liver histopathological alterations. The expressions of renal glucose transporter 9 (GLUT9), ATP-binding cassette subfamily G member 2 (ABCG2), organic anion transporter 1 (OAT1), phospho-janus kinase 2 (p-JAK2), p-signal transducer and activator of transcription 3 (p-STAT3), suppression of cytokine signaling 3 (SOCS3), NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and cleaved-cysteinyl aspartate specific proteinase-1 (cleaved-Cas-1) were detected by western blots. The potential protein targets and pathways of FZ intervention on HUA were predicted by network pharmacology. The constituents in FZ aqueous extract were analyzed by UPLC-MS. ResultsFZ reduced serum UA, CRE, BUN, and urinary albumin and increased urine UA, CRE levels in HUA mice. In addition, the treatment with FZ to HUA mice inhibited the elevated serum levels of XOD and ADA, and regulated renal urate transports including OAT1, GLUT9 and ABCG2. FZ also attenuated kidney inflammation and fibrosis and downregulated the expressions of IL-1β, p-JAK2, p-STAT3, SOCS3, IL-6, NLRP3, ASC, and cleaved-Cas-1. Thirteen compounds were identified in the FG, including L-phenylalanine, D-tryptophan, 3′-hydroxypuerarin, Puerarin, 3′-Methoxy Puerarin, Daidzin, Pueroside A, formononetin-8-C- [xylosyl (1→6)]-glucoside, Ononin, Alisol I 23-acetate, 16-oxo-alisol A, Alisol C and Alisol A. ConclusionFZ inhibits serum UA generation and promotes urine UA excretion as well as attenuates kidney inflammation and fibrosis in HUA mouse with nephropathy. The underlying mechanism of its action may be associated with suppression of the JAK2/STAT3 signaling pathway and NLRP3 inflammasome activation. This formula may offer a novel source for developing anti-HUA drugs.

Protective Effect of Chrysin Against Chlorpyrifos-induced Hepatotoxicity in Rats: Biochemical and Histopathological Approaches in a Sub-chronic Study.

Chrysin (CH) is one of the important natural flavonoids with antioxidant and anti-inflammatory activity. The aim of this study was to assess the protective effects of CH on biochemical indexes and histopathological changes in the liver of male Wistar rats exposed to chlorpyrifos (CPF). We induced sub-chronic toxicity in rats using CPF (10 mg/kg/day, orally) and administrated CH at 12.5, 25, and 50 mg/kg/day for 45 days. In this study, CPF increased liver enzyme activities compared with the control group (p < 0.05), and co-treated CH with CPF reduced them compared with the non-treated CPF group (p < 0.05). A significant reduction in the liver GSH concentration along with a significant elevation in the concentrations of MDA and NO in the CPF group was observed compared with the control group (p < 0.001). However, CH at a dose of 50 mg could reverse them nearly to the control group (p < 0.001). In the CPF, CPF + CH1, and CPF + CH2 groups, a marked (p < 0.05) increase was found in the serum concentration of IL-6 compared with the control animals. No significant changes were found in the IL-6 concentration of the CPF + CH3 compared with the controls. Moreover, the coadministration of CH plus CPF induced histopathological alterations in liver. These results suggest that CH attenuates hepatic enzymes and histopathological alterations induced by CPF via modulating oxidative stress and inflammatory indices in rats.

Green Synthesis of Zinc Oxide-Nanoparticles from Ziziphus Spina-Christi Leaves Extract: Characterization and Their Protective Effects Against Liver Disturbances in Adenine-Exposed Male Rats

Zinc oxide nanoparticles (ZnO-NPs) have a significant feature due to their uses in various fields including medicine, biosensors, food additives, and electronic materials. This study aimed to the green synthesis of ZnO-NPs using aqueous extract of Ziziphus-spina christi leaves (Sider) and evaluates its protective roles against liver disorders after adenine-exposed male rats. Thirty-six male rats (3 months in age and weighing 200 ± 5 g) were randomly divided into 6 equal groups as following: Control adenine, Ziziphus-spina christi, ZnO-NPs, adenine + Ziziphus-spina christi and adenine + ZnO-NPs for 30 days. At the end of 30 days, the activity of (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), superoxide dismutase (SOD) and concentrations of reduced glutathione (GSH) and nitric oxide (NO) were determined, as well as the liver histopathological alterations were investigated. Moreover, the body weight of all rats was measured over a week. The synthesized ZnO-NPs was characterized using several techniques. UV-Visible analysis showed a specific absorption peak at 362 nm. In Fourier Transform Infrared spectroscopy (FT-IR) absorption bands of Zn-O stretching bonding showed between 400 and 500 cm−1. Their crystallinity, hexagonal shape, size, and the specific surface area for the dry ZnO-NPs were also determined using the techniques of X-ray diffraction (XRD) and scanning electron microscopy (SEM) respectively. Results showed significant decreases in ALT, AST and ALP in both groups adenine + Ziziphus-spina christi leaves extract and adenine + ZnO-NPs in comparison to the adenine group (p &lt; 0.05), as well as significant increases in body weight. Significant decrease was also demonstrated in NO level associated with an increase in SOD, and GSH. Based on these results, it can be said that ZnO-NPs and Ziziphus-spina christi leaves effectively protect against adenine-induced liver disorders, these were confirmed by improvements marked in histological changes of liver tissue of rats. GRAPHICAL ABSTRACT

Biochemical, Hematological and Histopathological Alterations in Liver and Lung of Rats Due to Sub-chronic Inhalation Exposure to NPK 15.15.15 Fertilizer

The current study has been conducted to evaluate biochemical, hematological and histopathological alterations in rats following one month of inhalation exposure to NPK (nitrate, phosphate, potassium) 15.15.15 fertilizer. 24 male Wistar rats were randomly divided into four groups (A, B, C and D). Group A was served as control, whereas B, C and D groups have been exposed to aerosol of different doses (10 mg/m3, 30 mg/m3 and 50 mg/m3, respectively) of NPK 15.15.15 fertilizer during 30 min/day for one month. At the end of the experiment, rats were sacrificed. Blood samples were collected to evaluate biochemical and hematological parameters. Liver and lung tissues were served to evaluate oxidative stress statue and histopathological alterations.&#x0D; Our results showed that inhalation exposure of rats to NPK 15.15.15 fertilizers, especially at high dose (50 mg/m3) resulted in a significant (P = 0,05) elevation of biochemical hepatic markers: Aspartate aminotransferase and Alanine transaminase, and a highly significant (P = 0,01) elevation of alkaline phosphatase. In addition, there were significant changes in hematological parameters revealed mainly by a highly significant (P = 0,01) increase of lymphocytes in both groups C and D groups, and significant decreases (P = 0,05) in all of: red blood cells, hematocrit, and hemoglobin in rats of group D compared to control. Furthermore, the inhalation exposure of rats to NPK 15.15.15 fertilizers induced lung oxidative stress revealed by the reduction of anti-oxidant enzymes (Glutathione peroxidase, reduced glutathione and superoxide dismutase); besides we have observed significant histopathological alterations revealed mainly by inflammatory cell infiltration in liver and lung tissues.&#x0D; The inhalation exposure to important doses of NPK 15.15.15 fertilizer can damage the liver and lung tissues by altering biochemical, hematological and oxidative stress parameters.

Protective effect of flaxseed oil the on diazinon-induced hepatotoxicity in male rats

Here in, we investigated the possible hepatoprotective effects of flaxseed oil on Diazinon (DZN) induced oxidative stress in rat liver. Twenty-five adult male Wistar rats (180–200 g) were divided randomly into five groups: Control group (1 ml normal saline orally), DZN group (70 mg/kg/day, p.o.), flaxseed oil group (200 mg/kg/day, p.o.), and co- treatment groups (DZN 70 mg/kg/day plus flaxseed oil at doses of 100 and 200 mg/kg/day, respectively). Oxidative stress markers including liver and serum level of malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (TAC), and total thiol group (TTG) were analyzed. Also liver function tests such as serum Alanine aminotransferases (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) were evaluated. Hematoxylin and eosin (H&E) staining was used for liver histological study. Compared to control group, DZN significantly increased liver and serum level of MDA, CAT, TAC and TTG. Also, DZN increased serum ALT, AST, and ALP levels. Flaxseed oil consumption significantly improved oxidative stress status and liver functions tests. Theses effectiveness was completely dose dependent. Also, flaxceed oil ameliorates liver histopathological alterations induced by DZN. Our data demonstrated DZN induced liver toxicity through oxidative stress mechanisms. Flaxceed supplementation had liver protective effects by decreasing oxidative stress markers and improvement of antioxidative status. Also, flaxceed reduced the development of DZN-induced alterations in liver. It seems that flaxceed supplementation may have protective role in DZN-induced oxidative damage in hepatic tissues.

Renoprotective effects of zinc sulfate against transient liver ischemia/reperfusion injury in rats

ObjectivesLiver ischemia/reperfusion damage frequently occurs in setting of hepatic resection and liver transplantation. It leads to disturbance in remote organs such as heart, lung and kidneys. This study explored the consequences of hepatic ischemia/reperfusion on the oxidative stress parameters, biochemical factors, and histopathological alterations in the kidney's rats, as well as evaluated the role of zinc sulfate on above-mentioned parameters. Materials and methodsTwenty-eight male Wistar rats were accidently assigned into four groups (n = 7). They were Sham, ischemia/reperfusion, zinc sulfate pretreatment, and zinc sulfate pretreatment + ischemia/reperfusion groups. Sham group: obtained normal saline (2 ml/day, seven consecutive days), intraperitoneally, zinc sulfate pretreatment group: obtained zinc sulfate (5 mg/kg, seven consecutive days, intraperitoneally). Ischemia/reperfusion group: obtained normal saline as mentioned previous, then rats experienced the partial ischemia (%70) for 45 min followed by 60 min reperfusion. Zinc sulfate pretreatment group: obtained zinc sulfate as mentioned previous, then rats experience the partial ischemia/reperfusion as presented earlier. At the end of investigation, blood was withdrawn, liver and renal tissues were removed. Then, biochemical and oxidative stress parameters, and histological changes were evaluated in the mentioned tissues. ResultsThe findings of this experiment indicated that zinc sulfate markedly reduced the serum levels of liver and kidney function tests in relative to ischemia/reperfusion group. Also, antioxidant enzymes activity, ferric reducing antioxidant power, and nitric oxide significantly increased, while malondialdehyde level declined in the renal tissue of zinc sulfate + ischemia/reperfusion group compared to ischemia/reperfusion rats. Furthermore, zinc sulfate alleviated the liver and kidneys histopathological alterations following ischemia/reperfusion. ConclusionZinc sulfate ameliorated liver and kidney function, and improved oxidant-antioxidant balance in favor of antioxidants. It is suggested that zinc sulfate may be beneficial effects on hepato-renal injury after ischemia/reperfusion.

Exploration of Maternal and Fetal Toxicity Risks for Metronidazole-Related Teratogenicity and Hepatotoxicity through an Assessment in Albino Rats.

Metronidazole is the primary antimicrobial drug for treating acute and chronic vaginal pathogens during pregnancy; however, there has been insufficient research on placental disorders, early pregnancy loss, and preterm birth. Here, the potential activity of metronidazole on pregnancy outcomes was investigated. 130 mg/kg body weight of metronidazole was orally given individually to pregnant rats on gestation days 0-7, 7-14, and 0-20. Pregnancy outcome evaluations were carried out on gestation day 20. It was demonstrated that metronidazole could induce maternal and fetal hepatotoxicity. There is a significant increase in the activities of maternal hepatic enzymes (ALT, AST, and ALP), total cholesterol, and triglycerides compared with the control. These biochemical findings were evidenced by maternal and fetal liver histopathological alterations. Furthermore, metronidazole caused a significant decrease in the number of implantation sites and fetal viability, whereas it caused an increase in fetal lethality and the number of fetal resorptions. In addition, a significant decrease in fetal weight, placental weight, and placental diameter was estimated. Macroscopical examination revealed placental discoloration and hypotrophy in the labyrinth zone and the degeneration of the basal zone. The fetal defects are related to exencephaly, visceral hernias, and tail defects. These findings suggest that the administration of metroniazole during gestation interferes with embryonic implantation and fetal organogenesis and enhances placental pathology. We can also conclude that metronidazole has potential maternal and fetal risks and is unsafe during pregnancy. Additionally, it should be strictly advised and prescribed, and further consideration should be given to the associated health risks.

Chronic cold-stress induced histopathological changes, oxidative stress, and alterations in liver functions and nutrient composition of hybrid red tilapia and the potential protection of unsaturated fatty acids

The hybrid red tilapia (♂Oreochromis niloticus × ♀O. mossambicus) is a promising tilapia fish with high growth rate, market acceptability, and the ability to live in a wide range of salinities, but it is sensitive to low water temperature. Therefore, the objective of this experiment was to improve hybrid red tilapia resistance to chronic cold stress by increasing unsaturated fatty acids and evaluating their effects on fish body weight, hepatosomatic index (HSI), body nutrient composition, liver function enzymes, histopathological alterations, and biomarkers of oxidative stress in the gills and liver. For 98 days, fish were fed four diets based on two dietary fat sources: corn oil (a traditional source) and Aquafat-O® (a commercial product rich in high polyunsaturated fatty acids), in different ratios of 3:0 (T0), 2:1 (T1), 1:2 (T2), and 0:3 (T3), respectively. Subsequently, all groups (T0+, T1, T2, and T3) were subjected to water cold stress at 13 °C for 15 days, with half of the control group serving as a negative control (T0-; at a rearing water temperature of 25-26 °C). Chronic old stress caused significant reductions in fish body weight, HSI, aspartate transaminase and alanine transaminase activities, fat and energy contents, and oxidative stress biomarkers in the liver and gills. Red tilapia subjected to low temperatures showed severely altered histopathological conditions in the liver and gills. However, by gradually increasing the Aquafat-O® ratio in the diet, the negative effects of cold stress were mitigated. Thus, it could be concluded that the beneficial use of Aquafat-O® (as a promising fat source) at a percentage of up to 69.60 g kg-1 is necessary to cope with the cold-water stress for sensitive hybrid red tilapia.

Bromelain ameliorates D-galactosamine-induced acute liver injury: role of SIRT1/LKB1/AMPK, GSK3β/Nrf2 and NF-κB p65/TNF-α/caspase-8, -9 signalling pathways.

The present research focused on estimating, for the first time, the potential protective effects of bromelain against D-galactosamine-induced acute liver injury in rats as well as identifying the possible underlying mechanisms. Silymarin (100 mg/kg/day, p.o.) as a reference drug or bromelain (20 and 40 mg/kg/day, p.o.) were administered for 10 days, and on the 8th day of the experiment, a single dose of galactosamine (400 mg/kg/i.p.) induced acute liver injury. Pretreatment with bromelain improved liver functions and histopathological alterations induced by galactosamine. Bromelain ameliorated oxidative stress by inducing SIRT1 protein expression and increasing LKB1 content. This resulted in phosphorylating the AMPK/GSK3β axis, which stimulated Nrf2 activation in hepatic cells and thus increased the activity of its downstream antioxidant enzymes [HO-1 and NQO1]. Besides, bromelain exerted significant anti-apoptotic and anti-inflammatory effects by suppressing hepatic contents of TNF-α, NF-κB p65, as well as caspase-8 and caspase-9. The protective effects of bromelain40 were proved to be better than silymarin and bromelain20 in most of the assessed parameters. Our results highlight the significant hepatoprotective effects of bromelain against acute liver injury through modulation of SIRT1/LKB1/AMPK, GSK3β/Nrf2 signalling in addition to NF-κB p65/TNF-α/ caspase-8 and -9 pathway.

Mitigative Potential of Novel Lactobacillus plantarum TISTR 2076 against the Aflatoxins-Associated Oxidative Stress and Histopathological Alterations in Liver and Kidney of Broiler Chicks during the Entire Growth Period.

Aflatoxins are the secondary metabolites produced by Aspergillus flavus and Aspergillus parasiticus and have severe pathological effects on the health of human and animals. The present study was designed to investigate the toxicopathological changes induced by aflatoxins and mitigative potential of Lactobacillus plantarum in broiler birds. One hundred and eighty broiler chicks at one day of age was procured from the local market, and chicks were equally divided into six groups with thirty birds in each group. These birds were treated with aflatoxins (300 and 600 µg/kg) and Lactobacillus plantarum (1 × 108 cfu/kg of feed) in different combinations. The first group was kept as the control, and only a basal diet was provided to birds (BD). In the second group (AF1), the first level of aflatoxins (300 µg/kg) was fed to the birds. In the third group (AF2), the second level of aflatoxins (600 µg/kg) was fed to birds. In the fourth group (AF1LP), Lactobacillus plantarum was given with first level of aflatoxins. In the fifth group (AF2LP), Lactobacillus plantarum was given with the second level of aflatoxins, and in the 6th group (BDLP), Lactobacillus plantarum alone was fed to the chicks. This experimental study was continued for 42 days. Birds were slaughtered after 42 days, and different parameters were assessed. Parameters studied were gain in body weight, organ weight along with some histopathological, hematological, biochemical parameters and residues of aflatoxins in liver and kidney. Lactobacillus plantarum improved the body weight gain and restored the relative organ weight. Hepatic and renal biomarkers returned to normal concentrations, serum proteins were restored in combination group AF1LP, and partial amelioration was observed in the AF2LP group. Red blood cells, white blood cells, hemoglobin centration and packed cell volume became normalized in the AF1LP group, while partial amelioration was observed in the AF2LP group. LP also reduced the concentration of aflatoxin residues in liver kidney and improved the TAC concentrations. The results of this study elucidated the mitigative potential of Lactobacillus plantarum against serum biochemical, histopathological, hematological and toxicopathological changes induced by aflatoxins in the chicks.

Ivermectin ameliorate the toxic effect of dimethylhydrazine in male Wistar rats

Cancer is emerging as one of the most significant challenges to the human health. Ivermectin (IVM) is one of the most effective drugs in veterinary and human medicine. The purpose of this study was to evaluate the potential preventative effect of IVM against cytotoxicity induced by dimethylhydrazine (DMH) in Male Wistar rats. Three concentrations of IVM (0.25, 0.5 and 1 mg/kg) were utilized in this study. Liver function enzymes, inflammatory markers and histopathological alterations in liver and kidney tissues were investigated. Obtained data showed that the combination of DMH with each concentration of IVM increased the activity of liver enzymes (ALT, ALP, AST, and GGT) compared to control and DMH alone. RT-PCR findings showed upregulation in the level of INF-γ, IL-6, IL-1β, Cox1, and Cox2 genes compared to control. In contrast, IL-6 gene was down-regulated. The levels of genes expression were down-regulated with combined DMH with medium and high concentrations compared to DMH alone. Microscopic analysis demonstrated histological alterations in the liver and kidney of rats treated with DMH. Combinations of DMH either with medium or high concentration resulted in less pathological features in both liver and kidney tissues. In conclusion, this study showed that IVM mitigated the toxic effects of DMH on the liver and kidney of male Wistar rats.

Histopathological Alterations in Liver of Male Rabbits Exposed to Deltamethrin and the ameliorative Effect of Folic Acid

Histopathological Alterations in Liver of Male Rabbits Exposed to Deltamethrin and the ameliorative Effect of Folic Acid