Liver GSH Levels Research Articles

Iristectorin A Ameliorates Cisplatin-Induced Hepatorenal Injury in Mice Through Modulation of the Nrf2/HO-1 Signaling Pathway.

Cisplatin (CIS) is a chemotherapeutic agent frequently used in cancer treatment. However, depending on the dosage and duration of use, CIS can lead to hepatotoxicity and nephrotoxicity. Iristectorin A (IRIS), a natural flavonoid, has been found to exhibit antioxidant and protective effects. In this paper, we scrutinized the effects and molecular mechanisms of the IRIS on CIS-induced liver and kidney damage in mice. IRIS administration alleviated CIS-induced elevations in AST, ALT, ALP, BUN, and creatinine levels by approximately 12%, 15%, 11%, 21%, and 15%, respectively. It also inhibited liver and kidney MDA levels by approximately 29% and 28%, while enhancing liver and kidney GSH, SOD, and CAT levels by 47%-60%, 85%-70%, and 90%-55%, respectively. IRIS enhanced liver and kidney mRNA expression levels of Nrf2 (by approximately 1.6- and 1.5-fold, respectively), HO-1 (by 1.5- and 1.5-fold, respectively), and Bcl-2 (by 1.5- and 1.4-fold, respectively). In addition, IRIS suppressed the mRNA expression levels of NF-κB (by 0.7- and 0.7-fold), TNF-α (by 0.7- and 0.7-fold), Bax (by 0.8- and 0.7-fold), and Cas-3 (by 0.9- and 0.7-fold). Protein expression analysis revealed that IRIS increased Nrf2 (by 1.5- to 1.2-fold) and Bcl-2 levels (by 1.3- to 1.7-fold), and reduced Bax (by 0.7- to 0.8-fold) and Cas-3 (by 0.8- and 0.8-fold) levels altered by CIS treatment. Moreover, IRIS administration prevented histopathological changes in the liver and kidney caused by CIS. Ultimately, IRIS was found to substantially mitigate CIS-induced hepatorenal injury by targeting oxidative stress, inflammation, and apoptosis through regulation of the Nrf2/HO-1 signaling pathway. Therefore, IRIS holds potential as a therapeutic adjuvant in the use of CIS.

Preparation of gallic acid-loaded chitosan nanoparticles and their chemoprotective effects on N-ethyl-N-nitrosourea-induced hepatotoxicity and mortality in rats.

N-ethyl-N-nitrosourea (ENU) as n-nitrosamine and alkylating agent, ubiquitous within living cells and in the environment can act as a full carcinogen and induce tumor formation in various tissues such as liver. In this study, gallic acid-loaded chitosan nanoparticles (GANPs) were synthesized and evaluated for their chemopreventive effect against ENU-induced hepatotoxicity and mortality in rats. Twenty-four male Wistar rats were divided into four groups including: control, ENU (single doses of 50mg/kg via intraperitoneal injection), GA + ENU and GANPs + ENU. Animals were orally pretreated with GA (50 mg/kg) and GANPs (50 mg/kg) for 30 days, and liver injuries induced by ENU on the 31st day of study. After ENU administration, weight changes and mortality were monitored during 30 days, and then the animals were sacrificed and alpha-fetoprotein (AFP) as a tumor marker, liver function tests (ALT, AST and ALP), oxidative stress markers (GSH and MDA), mitochondrial toxicity parameters, and histopathological assessment were evaluated. Except for AFP and MDA, ENU caused significant elevation of liver enzymes, mitochondrial ROS formation, collapse of mitochondrial membrane potential depletion of GSH, histopathological abnormalities and mortality in rats. Our data showed that GANPs significantly increased the survival of rats by up to 66%, delayed in death time and prevented weight changes after exposure to ENU. Moreover, GANPs restored liver enzyme levels, ROS formation, mitochondrial dysfunction, GSH levels, and histopathological abnormalities towards normal. Our findings suggest that GANPs revealed a significant protective effect against deadly toxicity induced by ENU as an alkylating full carcinogen agent in liver tissue.

Effects of CdSe/ZnS-QD525 on oxidative stress in the liver and kidneys of mice

Nanotechnology is widely applied in biomedicine and pharmacy. It is necessary to systematic analysis the potential hazardous of QDs s to ensure their safe usage. Here, we analyzed the in vivo oxidative stress of CdSe/ZnS-QD525 at different time via intraperitoneal injection of CdSe/ZnS-QD525 in male KM mice. The results showed that in 30 nmol/kg dose group, the GSH levels of liver and kidneys were significantly decreased at day 11 (p < 0.05), while the GSH levels in liver on day 33 and in kidneys on day 22 were significantly increased (p < 0.01). The SOD activity in liver was significantly reduced (p < 0.01) of the 30 nmol/kg dose group on day 22, and the SOD activity in liver of low, middle and high dose groups treated for 33 days was significantly increased (p < 0.01). The CAT activity in liver of 30 nmol/kg and 150 nmol/kg dose groups on day 33 was significantly lower (p < 0.05) than the control group, the CAT activity was significantly increased (p < 0.05) of 30 nmol/kg dose group in kidneys. Therefore, this study indicated that CdSe/ZnS-QD525 induced oxidative damage, and caused related toxicity, which provided valuable information in evaluating the biological safety of QDs.

Extraction and characterization of hepatoprotective polysaccharides from Anoectochilus roxburghii against CCl4-induced liver injury via regulating lipid metabolism and the gut microbiota

Anoectochilus roxburghii polysaccharides exhibit notable hepatoprotective effects, but the underlying substance basis and mechanisms remain unknown. In this study, four new polysaccharides named ARP-1a, ARP-1b, ARP-2a and ARP-2b, were isolated from A. roxburghii. Their structural characteristics were systematically analyzed using HPGPC, HPLC, GC–MS, IR and NMR analysis. ARP-1a, the leading polysaccharide isolated from A. roxburghii, was further evaluated for its hepatoprotective effects on acute liver injury mice induced by CCl4. ARP-1a significantly reduced the serum ALT, AST, TNF-α, IL-1β and IL-6 levels, liver MDA content, and increased the SOD and CAT activities and GSH level in liver. H&E staining revealed that ARP-1a pretreatment could markedly relieve liver injury. Further mechanism exploration indicated that ARP-1a could relieve CCl4-induced oxidative damage through activating the Nrf2 signaling. In addition, metabolomics, lipidomics and 16S rRNA amplicon sequencing were used to elucidate the underlying mechanisms of ARP-1a. Multi-omics analysis indicated that ARP-1a exerted hepatoprotective effect against CCl4-induced acute liver injury by regulating lipid metabolism and modulating the gut microbiota. In conclusion, the above results suggest that ARP-1a can be considered a promising and safe candidate for hepatoprotective drug, as well as a potential prebiotic for maintaining intestinal homeostasis and promoting human intestinal health.

Validation of Salamander Dermal Mucus Swabs as a Novel, Nonlethal Approach for Amphibian Metabolomics and Glutathione Analysis Following Pesticide Exposure.

Evaluating biomarkers of stress in amphibians is critical to conservation, yet current techniques are often destructive and/or time-consuming, which limits ease of use. In the present study, we validate the use of dermal swabs in spotted salamanders (Ambystoma maculatum) for biochemical profiling, as well as glutathione (GSH) stress response following pesticide exposure. Thirty-three purchased spotted salamanders were acclimated to laboratory conditions at Washington College (Chestertown, MD, USA) for 4 weeks. Following acclimation, salamanders were randomly sorted into three groups for an 8-h pesticide exposure on soil: control with no pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), or chlorpyrifos. Before and after exposure, mucus samples were obtained by gently rubbing a polyester-tipped swab 50 times across the ventral and dorsal surfaces. Salamanders were humanely euthanized and dissected to remove the brain for acetylcholinesterase and liver for GSH and hepatic metabolome analyses, and a whole-body tissue homogenate was used for pesticide quantification. Levels of GSH were present in lower quantities on dermal swabs relative to liver tissues for chlorpyrifos, 2,4-D, and control treatments. However, 2,4-D exposures demonstrated a large effect size increase for GSH levels in livers (Cohen's d = 0.925, p = 0.036). Other GSH increases were statistically insignificant, and effect sizes were characterized as small for 2,4-D mucosal swabs (d = 0.36), medium for chlorpyrifos mucosal swabs (d = 0.713), and negligible for chlorpyrifos liver levels (d = 0.012). The metabolomics analyses indicated that the urea cycle, alanine, and glutamate metabolism biological pathways were perturbed by both sets of pesticide exposures. Obtaining mucus samples through dermal swabbing in amphibians is a viable technique for evaluating health in these imperiled taxa. Environ Toxicol Chem 2024;43:1126-1137. © 2024 SETAC.

Cynara Cardunculus Flavonoids-rich Fraction Alleviates Liver Injury in Mice Overconsumed Fructose Model.

Non-alcoholic Fatty liver disease (NAFLD) is becoming a major global health burden in the world. Cynara cardunculus is an edible plant growing wild in the North of Algeria. Its potential as a source of health-promoting compounds is still underexplored. This study aimed to explore the preventive effect of Cynara cardunculus (C.cardunculus) on the NAFLD model. Total flavonoid contents (TFC) and in vitro antioxidant effects of butanolic (n- BuTOH) and ethyl acetate (EtOAc) fractions on scavenging the ABTS+ radical, inhibition of lipid peroxidation and reducing power proprieties were assessed. The n-ButOH fraction showed the highest TFC and antioxidant capacity in all realized assays. This fraction is used for anti- NAFLD experiments. Adult male Albinos mice were divided into four groups. Group 1 was normal control. Group 2 was watered with 30% of fructose for three weeks to induce the NAFLD model. Group 3 and Group 4 were co-treated with C. cardunculus n-ButOH fractions and Atorvastatin, respectively for three weeks. Blood and livers were collected for biochemical and histological analysis. The C. cardunculus n-ButOH fractions significantly restored levels of transaminases, triglycerides, cholesterol, LDL, glucose and uric acid. The n-ButOH fraction exerted an improving effect on the body and liver weight and liver index. It also significantly corrected the imbalance in liver MDA and GSH levels. The n-ButOH fractions further ameliorated abnormalities in liver histology through suppression of lipid droplet accumulation. This research proves that the flavonoid-rich fraction of C. cardunculus has protective activity against high fructose intake in mice via reversing hyperlipidemia and boosting liver antioxidant capacity.

Effects of naringenin on oxidative damage and apoptosis in liver and kidney in rats subjected to chronic mercury chloride.

Mercury chloride is a type of heavy metal that causes the formation of free radicals, causing hepatotoxicity, nephrotoxicity and apoptosis. In this study, the effects of naringenin on oxidative stress and apoptosis in the liver and kidney of rats exposed to mercury chloride were investigated. In the study, 41 2-month-old male Wistar-Albino rats were divided into five groups. Accordingly, group 1 was set as control group, group 2 as naringenin-100, group 3 as mercury chloride, group 4 as mercury chloride + naringenin-50, and group 5 as mercury chloride + naringenin-100. For the interventions, 1 mL/kg saline was administered to the control, 0.4 mg/kg/day mercury (II) chloride to the mercury chloride groups by i.p., and 50 and 100 mg/kg/day naringenin prepared in corn oil to the naringenin groups by gavage. All the interventions lasted for 20 days. Mercury chloride administration was initiated 1 h following the administration of naringenin. When mercury chloride and the control group were compared, a significant increase in plasma urea, liver and kidney malondialdehyde (MDA) levels, in kidney superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) activities (p < .001), and a significant decrease in liver and kidney glutathione (GSH) levels (p < .001), in liver catalase (CAT) activity (p < .01) were observed. In addition, histopathological changes and a significant increase in caspase-3 levels were detected (p < .05). When mercury chloride and treatment groups were compared, the administration of naringenin caused a decrease aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) (p < .01), urea, creatinine levels (p < .001) in plasma, MDA levels in liver and kidney, SOD, GSH-Px, GST activities in kidney (p < .001), and increased GSH levels in liver and kidney. The addition of naringenin-100 increased GSH levels above the control (p < .001). The administration of naringenin was also decreased histopathological changes and caspase-3 levels (p < .05). Accordingly, it was determined that naringenin is protective and therapeutic against mercury chloride-induced oxidative damage and apoptosis in the liver and kidney, and 100 mg/kg naringenin is more effective in preventing histopathological changes and apoptosis.

Investigation of the effects of nanoemulsion formulation containing glycyrrhizin in Streptozotocin-induced diabetic rats

This study aims to prepare and in vitro and in vivo characterize nanoemulsion formulation containing GLY (GLY-NE). Firstly, the NE formulation was prepared and in vitro characterized. Later, the hypoglycemic and antioxidant effects of GLY-NE formulations in STZ-induced diabetic rats were investigated. Also, histopathological evaluation was performed. The droplet sizes of blank NE (B-NE; 110.75 ± 9.60) and GLY-NE (126.44 ± 3.86) were in the nano-size range. Furthermore, PDI values of B-NE and GLY-NE formulations were less than 0.3. The zeta potential values of B-NE and GLY-NE were (−)19.02 ± 1.18 mV and (−) 20.52 ± 0.83 mV, respectively. At the end of the 21st day, comparing the same dose groups administered GLY or GLY-NE, the blood glucose levels of the diabetic rats administered GLY-NE (D-GLY-NE groups) were lower than the diabetic rats administered GLY (D-GLY groups). Furthermore, the blood glucose level of D-GLY-NE (40 mg/kg) was significantly lower than that of D-GLY (40 mg/kg; p < 0.05). Compared with the diabetic control, the serum ALT and AST levels and liver MDA of the diabetic rats treated with GLY or GLY-NE (for all doses) were significantly decreased, while the liver SOD activity and GSH levels were significantly increased (p < 0.05). The NE formulation may be a potential dosage form for oral delivery of GLY.

Expected adverse health influences due to exposure to glyphosate-based herbicide (GBH) and its environmental outcomes using Wistar rats as experimental animals

A sum of 32 Wistar rats were divided into four equal groups, each containing 8 rats. Study animals were freely subject to normal rodent diet and tap water. One group was put as control. The applied agents were exposed to glyphosate-based herbicide (GBH-400 mg kg–1) GSH (nmol g–1 tissue), (GBH-600 mg kg–1) GSH (nmol g–1 tissue) and (GBH-850 mg kg–1) GSH (nmol g–1 tissue) once per day as oral gavage for 6 weeks. Study results clearly revealed that (GBH) significantly (p≤0.05) decreased the levels of GSH in liver, kidney, and brain tissues, due to many reasons including poor diet, chronic disease, infection and constant stress, besides aging. Biological negative influences of glyphosate herbicide through the scientific community, including government and non-government organizations have increased their interest in detecting and controlling the environmental agents responsible for damages to the human health and sustainability of the ecosystems.

Endotoxin lipopolysaccharide (LPS)-induced peripheral inflammation and its impact on brain and liver function

Endotoxin Lipopolysaccharide (LPS) induces an innate immune response and activates sickness behavior. During neuroinflammation, the activated microglial cells change its morphology and release various chemicals that could be harmful such as nitric oxide (NO), reactive oxygen species (ROS) and enzymes for proteolysis. Through the buildup of free radicals and ROS, these neuroinflammations can also result in oxidative stress. This ROS reacts with cellular macromolecules, triggering a cascade that results in membrane porosity caused by membrane lipid peroxidation (LPO), which is measured by the quantity of malondialdehyde (MDA). On LPS challenge, the complex behaviour that decreased common activities and explorations, is noticed and with rising anxiety, cognitive impairment and decreased social activities. It also decreased closed arm time, although closed arm entries were higher which may be related to the increased locomotion. It raised open arm time and open arm entries, suggesting of reduced anxiety and also increased exploratory behaviour. AChE and nNOS were increased in the forebrain part. Reduction in brainstem and MDA activity decreased on both forebrain and brain stem. MDA in the liver increased by LPS challenge indicating upregulated hepatic tissue damage and oxidative stress. As a result of LPS-induced lipid peroxidation and oxidative stress, brain Glutathione (GSH), a substrate for cytosolic Glutathione peroxidase, increased in the forebrain and decreased in the brainstem. Decreased scavenging of ROS was indicated by the LPS-induced decrease in liver GSH levels.

The kinetics of glutathione in the gastrointestinal tract of weaned piglets supplemented with different doses of dietary reduced glutathione.

This study aimed to investigate the kinetics of dietary GSH in the gastrointestinal tract and the effect of GSH on the intestinal redox status of weaned piglets. Forty-eight piglets with an average age of 26 days and an average body weight of 7.7 kg were used in this study. The piglets were divided into three treatment groups including the control group with a basal diet (CON) and two GSH groups with a basal diet supplemented with 0.1% GSH (LGSH) and 1.0% GSH (HGSH), respectively. The basal diet did not contain any GSH. The experiment lasted for 14 days, with eight animals sampled from each group on d5 and 14. The parts of 0-5%, 5-75%, and 75-100% of the length of the small intestine were assigned to SI1, SI2, and SI3. The results showed that GSH almost completely disappeared from the digesta at SI2. However, no difference in the GSH level in mucosa, liver, and blood erythrocytes was found. The level of cysteine (CYS) in SI1 digesta was significantly higher in HGSH than CON and LGSH on d14, and similar findings were observed for cystine (CYSS) in SI3 digesta on d5. The CYSS level in HGSH was also significantly higher than LGSH in the stomach on d14, while no CYS or CYSS was detected in the stomach for control animals, indicating the breakdown of GSH to CYS already occurred in the stomach. Irrespective of the dietary treatment, the CYS level on d14 and the CYSS level on d5 and 14 were increased when moving more distally into the gastrointestinal tract. Furthermore, the mucosal CYS level was significantly increased at SI1 in the LGSH and HGSH group compared with CON on d5. Glutathione disulfide (GSSG) was recovered in the diets and digesta from the LGSH and HGSH group, which could demonstrate the auto-oxidation of GSH. It is, therefore, concluded that GSH supplementation could not increase the small intestinal mucosal GSH level of weaned piglets, and this could potentially relate to the kinetics of GSH in the digestive tract, where GSH seemed to be prone to the breakdown to CYS and CYSS and the auto-oxidation to GSSG.

Baicalein Protects Against Iron Overload Induced Liver Dysfunction in Thalassemic Mice

Liver iron overload is a common and serious organ injury in β-thalassemia patients. Ferroptosis has been shown to play a crucial role in the pathological injury in iron overloaded hepatocytes. In our study, we focused on the protective effects of baicalein, a natural, active flavone extracted from an herb used in traditional Chinese medicine against RSL3-induced ferroptosis in hepatocytes and high iron diet (HID) induced liver iron-overload in a murine β654-thalassemia model. In vitro, the effects of baicalein on RSL3-induced hepatocyte ferroptosis were examined by testing ferroptosis related genes, protein, and the GSH, MDA, iron ion level by RT-PCR, Western blot and the commercial kits respectively. The anti-iron overload injury effects of baicalein were assessed in a β654-thalassemia mouse model of high iron diet induced liver injury by the same method In vitro experiments. Here, we found that baicalein could reverse cell ferroptosis in hepatocytes treated with RSL3. Importantly, changes in the iron ion content, and MDA and GSH levels in β654-thalassemia mouse livers were significantly restored by baicalein. Mechanistically, baicalein may activated the NRF2 antioxidant pathway and increased the expression of GPX4 in vivo and In vitro. We concluded that baicalein is a potential therapeutic drug for the treatment of iron overload in β-thalassemia.

Short-term arecoline exposure affected the systemic health state of mice, in which gut microbes played an important role

Arecoline is a critical bioactive component in areca nuts with toxicity and pharmacological activities. However, its effects on body health remain unclear. Here, we investigated the effects of arecoline on physiologic and biochemical parameters in mouse serum, liver, brain, and intestine. The effect of arecoline on gut microbiota was investigated based on shotgun metagenomic sequencing. The results showed that arecoline promoted lipid metabolism in mice, manifested as significantly reduced serum TC and TG and liver TC levels and a reduction in abdominal fat accumulation. Arecoline intake significantly modulated the neurotransmitters 5-HT and NE levels in the brain. Notably, arecoline intervention significantly increased serum IL-6 and LPS levels, leading to inflammation in the body. High-dose arecoline significantly reduced liver GSH levels and increased MDA levels, which led to oxidative stress in the liver. Arecoline intake promoted the release of intestinal IL-6 and IL-1β, causing intestinal injury. In addition, we observed a significant response of gut microbiota to arecoline intake, reflecting significant changes in diversity and function of the gut microbes. Further mechanistic exploration suggested that arecoline intake can regulate gut microbes and ultimately affect the host's health. This study provided technical help for the pharmacochemical application and toxicity control of arecoline.

Magnesium Supplementation Alleviates the Toxic Effects of Silica Nanoparticles on the Kidneys, Liver, and Adrenal Glands in Rats.

Concerns regarding the possible hazards to human health have been raised by the growing usage of silica nanoparticles (SiNPs) in a variety of applications, including industrial, agricultural, and medical applications. This in vivo subchronic study was conducted to assess the following: (1) the toxicity of orally administered SiNPs on the liver, kidneys, and adrenal glands; (2) the relationship between SiNPs exposure and oxidative stress; and (3) the role of magnesium in mitigating these toxic effects. A total of 24 Sprague Dawley male adult rats were divided equally into four groups, as follows: control group, magnesium (Mg) group (50 mg/kg/d), SiNPs group (100 mg/kg/d), and SiNPs+ Mg group. Rats were treated with SiNPs by oral gavage for 90 days. The liver transaminases, serum creatinine, and cortisol levels were evaluated. The tissue malondialdehyde (MDA) and reduced glutathione (GSH) levels were measured. Additionally, the weight of the organs and the histopathological changes were examined. Our results demonstrated that SiNPs exposure caused increased weight in the kidneys and adrenal glands. Exposure to SiNPs was also associated with significant alterations in liver transaminases, serum creatinine, cortisol, MDA, and GSH. Additionally, histopathological changes were significantly reported in the liver, kidneys, and adrenal glands of SiNPs-treated rats. Notably, when we compared the control group with the treated groups with SiNPs and Mg, the results revealed that magnesium could mitigate SiNPs-induced biochemical and histopathologic changes, confirming its effective role as an antioxidant that reduced the accumulation of SiNPs in tissues, and that it returns the levels of liver transaminases, serum creatinine, cortisol, MDA, and GSH to almost normal values.

Free and bound phenols from Cymbopogon citratus mitigated hepatocellular injury in streptozotocin-induced type 1 diabetic male rats via decrease in oxidative stress, inflammation, and other risk markers

Background/AimDiabetes mellitus is a debilitating disease still prevailing in the developing world. This study aimed to examine the protective potentials of Cymbopogon citratus extracts (crude (CCC), free (CFP), and bound phenol (CBP) fractions), in streptozotocin (STZ)-induced type 1 diabetic male rats. MethodsForty-five (45) animals of about 3–4 months were used for the study. About forty animals were induced with STZ. After induction and confirmation of diabetes, animals were grouped (five animals per group) into nine groups; group 1 (Control), group 2 received 50 mg/kg body weight (bw) (STZ). Groups 3, 4 and 5 were healthy animals and received C. citratus extracts (200 mg/kg bw CCC, 100 mg/kg bw CFP, and 100 mg/kg bw CBP) respectively; while groups 6 – 9 were diabetic group (induced with STZ) and later treated with C. citratus extracts (200 mg/kg bw CCC, 100 mg/kg bw CFP, 100 mg/kg bw CBP, and metformin (200 mg/kg bw) respectively for 14 days. Then, the animals were euthanized, blood/serum was collected, liver samples were collected and divided into two; for biochemical and histopathological studies. Liver biomarkers (ALT, AST, ALP, GGT), fructose-1,6-bisphosphatase, hexokinase, antioxidant enzymes (SOD, CAT, and GST) activities, albumin, bilirubin, hepatic glucose, GSH, MDA, pro-and anti-inflammatory cytokines concentrations, were estimated using standard protocols. ResultsOur results revealed that C. citratus extracts counteracted the deleterious effects of type 1 diabetes induction with STZ by optimizing the liver biomarkers, antioxidants enzymes, MDA and GSH levels, reducing the levels of pro-inflammatory cytokines and increasing anti-inflammatory. ConclusionOur results correlated with previous researches; the free phenols fraction revealed brilliant results above others. These suggested that C. citratus could serve as an alternative therapy in ameliorating liver complications linked to oxidative damage and inflammation in STZ-induced type-1 diabetes.

The effect of vitamin C supplementation on favipiravir-induced oxidative stress and proinflammatory damage in livers and kidneys of rats

Background: Favipiravir (FPV), an effective antiviral agent, is a drug used to treat influenza and COVID-19 by inhibiting the RNA-dependent RNA polymerase (RdRp) of RNA viruses. FPV has the potential to increase oxidative stress and organ damage. The purpose of this study was to demonstrate the oxidative stress and inflammation caused by FPV in the liver and kidneys of rats, as well as to investigate the curative effects of vitamin C (VitC). Methods: A total of 40 Sprague–Dawley male rats were randomly and equally divided into the following five groups: 1st; Control, 2nd; FPV = 20 mg/kg, 3rd; FPV = 100 mg/kg, 4th; FPV = 20 mg/kg + VitC (150 mg/kg), and 5th; FPV = 100 mg/kg + VitC (150 mg/kg) groups. Rats were given either FPV (orally) or FPV plus VitC (intramuscular) for 14 days. Rat blood, liver, and kidney samples were collected at 15 days to be analyzed for oxidative and histological changes. Results: FPV administration resulted in an increase in proinflammatory cytokines (TNF-α and IL-6) in the liver and kidney, as well as oxidative and histopathologic damage. FPV increased TBARS levels significantly (p < .05) and decreased GSH and CAT levels in liver and kidney tissues but had no effect on SOD activity. VitC supplementation significantly reduced TNF-a, IL-6, and TBARS levels while increasing GSH and CAT levels (p < .05). Furthermore, VitC significantly attenuated FPV-induced histopathological alterations associated with oxidative stress and inflammation in the liver and kidney tissues (p < .05). Conclusion: FPV caused liver and kidney damage in rats. In contrast, co-administration of FPV with VitC improved FPV-induced oxidative, pro-inflammatory, and histopathological changes.

Alteration of Glutathione and Antioxidant Status with Exercise in Unfed and Refed Rats

The influences of food deprivation and refeeding on glutathione (GSH) status, antioxidant enzyme activity and lipid peroxidation in response to an acute bout of exercise were investigated in the liver and skeletal muscles of male Sprague-Dawley rats randomly divided into three groups: starved for 48 h without refeeding; starved for 48 h and refed for 24 or 48 h. Half of each group of rats was exercised on a treadmill until exhaustion and killed immediately, whereas the other half group was killed at rest. Food-deprived rats had significantly lower liver GSH concentration and GSH:glutathione disulfide (GSSG) ratio. Malondialdehyde concentrations in the liver and skeletal muscle were both higher in the starved than in the refed rats (P < 0.05). Refed rats had significantly greater liver GSH level, γ-glutamylcysteine synthetase and glucose 6-phosphate dehydrogenase activities and plasma insulin concentration than unfed rats. Exercised 24- and 48-h refed rats had 27% and 31% lower liver GSH (P < 0.05), respectively, and a 21% lower GSH:GSSG ratio (P < 0.05) than their rested counterparts. Plasma insulin concentrations were significantly lower, whereas glucagon concentrations were greater in the exercised than in the rested rats. Muscle GSH concentration was significantly lower in the food-deprived than in the refed rats (P < 0.05) but was unaffected by exercise. Exercised 24-h refed rats had significantly elevated muscle GSSG concentration compared with rested rats, along with a higher GSH peroxidase and a lower γ-glutamyltranspeptidase activity (P < 0.05). These data indicate that both food deprivation-refeeding and exhaustive exercise influence liver and skeletal muscle glutathione status and that these changes may be controlled by hepatic glutathione synthesis and release due to hormonal stimulation.

The glutathione system state in rats exposed to ethanol intoxication, its combination with caffeine and modified photoperiod

Objective. To study the content of reduced glutathione (GSH), activities of glutathione peroxidase (GP) and glutathione-S-transferase enzymes (GST) in blood and liver of rats exposed to subacute alcohol intoxication, its combination with caffeine intake or constant light exposure, and the possibility of their correction with melatonin.Materials and methods. Experiments were performed on 42 male rats weighing 180-200 g kept under standard conditions of the vivarium and artificial equinox. Alcohol intoxication was induced by intragastric administration 40 % ethanol at a dose of 7 ml/kg of body weight for 7 days. Caffeine was administered by gavage at a dose of 30 mg/kg of body weight.Results. Ethanol poisoning and its combination with caffeine intake or exposure to constant light resulted in a decrease in GSH level and GP activity in RBCs and liver, besides the combination of ethanol+light resulted in more pronounced depletion of the parameters. The combination of ethanol with caffeine resulted in less reduction of GSH level in the blood (by 25%) but more depletion of GSH in the liver (by 45% vs. control) than in ethanol-treated rats. There was an elevation of GST activity in the liver of all groups of alcoholized animals. Administration of 5 mg/kg melatonin for 7 days limited depletion in GSH and prevented the changes in GP and GST activities in the blood and liver of all groups of animals.Conclusions. Melatonin administration prevented ethanol-induced toxicity in rats exposed to ethanol and its combination with caffeine or constant light for 7 days by limiting the depletion in GSH and preventing the changes in GP and GST activities in the blood and liver of all groups of animals.

Ammonia toxicity in Nile tilapia: Potential role of dietary baicalin on biochemical profile, antioxidant status and inflammatory gene expression

The privileges of dietary baicalin intervention as a prophylaxis were assessed in Nile tilapia (Oreochromis niloticus) pre and post-acute ammonia challenge. The experimental trial lasted for 4 weeks, the first group served as a control (fed a basal diet), while, the second group received diet supplemented with baicalin (0.8 g/kg diet). The third group was fed a basal diet and exposed to acute ammonia toxicity in the last week. Meanwhile, the fourth group fed diet supplemented with baicalin (0.8 g/kg diet), then exposed to unionized ammonia challenge (5 mg/L) in the last week. Dietary baicalin notably augmented immune indicators (lysozyme, respiratory burst activity, phagocytic activity assay, and immunoglobulin (Ig) and tissue antioxidant biomarkers (total antioxidant capacity (TAC), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)). Meanwhile, it decreased malondialdehyde (MDA), hepato-renal indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, uric acid, creatinine), and stress indicators including glucose, cholesterol, triglycerides, and cortisol. Ammonia exposure significantly elevated stress parameters and MDA, but lessened SOD, GSH, CAT, and TAC levels in liver, gills, and kidneys tissue. Dietary baicalin and ammonia exposure induced interaction impacts on urea, creatinine, cortisol, glucose, lysozyme, alanine aminotransferase (ALT), aspartate aminotransferase (AST). Prior to ammonia exposure, baicalin administration clearly decreased urea. Fish fed enriched diet with - baicalin showed no changes in stress biomarkers before ammonia exposure, meanwhile reduced it after the ammonia challenge. Dietary baicalin alleviated fluctuations induced by ammonia in all above-mentioned parameters. And alleviated the altered gene expression for Hsp70, Nf-κB, Myd88, traf6, Nrf2, Ho-1, Il-1β, Il-8, TNF-α, and TLR-4 induced by ammonia toxicity. Taken together, it has been recommended to use baicalin for 3 weeks to mitigate ammonia-induced-oxidative damage, immune impairment, stress condition, hepato-renal failure, antioxidant and inflammatory gene expression in O. niloticus.

Rosemary and CoQ10 Alleviated the Detrimental Effects of Concomitant Administration of Acetaminophen and Carbamazepine by Accelerating Their Metabolism and Elimination

BACKGROUND: The interaction of carbamazepine (CBZ) and acetaminophen (APAP) could result in hepatic failure and mortality. This study was conducted to analyzed the potential of rosemary ethanol extract (REE) or coenzyme Q10 (CoQ10) to alleviate the interactions between CBZ and APAP.METHODS: Fourty-eight adult male rats were treated differently based on the assigned groups. Oxidative stress parameters, including malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase, and glutathione S-transferase (GST), and the expression levels of CYP3A4, CYP2E1, IL-6, TNF-α, and IL-1B in the liver were estimated. In addition, the histopathology of liver was examined and the plasma clearance rate of CBZ and APAP was estimated.RESULTS: Combination of CBZ and APAP significantly elevated alanine aminotransferase (ALT) activity and hepatic MDA, and reduced the activities of GPx, GST, and GSH level in liver. The gene expression of CYP3A4 and CYP2E1 was upregulated by CBZ and CoQ10, respectively. The expression of IL-6 has decreased in the groups treated with CBZ alone or in combination with APAP. TNF-α expression was significantly downregulated in the groups treated with CBZ, APAP, REE, CoQ10, or combination CBZ and APAP. The liver from CBZ and APAP combination group showed centrolobular degeneration and necrosis. REE and CoQ10 were able to alleviate most of these detrimental effects. The combined administration of CBZ and APAP extended the plasma clearance time of APAP and CBZ from 6 to 24 and from 9 to 24 hours, respectively.CONCLUSION: REE and CoQ10 alleviated the detrimental effects of the combination of CBZ and APAP through enhancing the cellular antioxidant milieu, induction of metabolizing enzymes, reduction of the plasma half-life of APAP and CBZ preventing their accumulation and potential interaction.KEYWORDS: acetaminophen, antioxidants, carbamazepine, CoQ10, CYP3A4, CYP2E1, glutathione, lipid peroxidation, rosemary