Rutin mitigates perfluorooctanoic acid-induced liver injury via modulation of oxidative stress, apoptosis, and inflammation.

Objectives: Perfluorooctanoic acid (PFOA) is a persistent organic pollutant (POP), broadly present in the environment. Due to long biological half-life, it is accumulated in the body, especially the liver, causing hepatocellular damage. This study was designed to assess the effects of rutin on PFOA-induced liver damage in rats. Materials and Methods: Male Wistar rats were exposed to PFOA (10 mg/kg/day) alone, or in combination with different doses of rutin (25, 50, and 100 mg/kg/day) by oral gavage for 4 weeks. Results: PFOA altered the levels of liver enzymes, induced a notable change in the tissue structure of the liver, caused some levels of mitochondrial dysfunction, and increased the expression of pro-apoptotic and pro-inflammatory genes. Co-treatment with rutin mitigated the PFOA-induced elevation of liver enzymes, histopathological defects, oxidative damage, and mitochondrial dysfunction. In addition, rutin declined the stimulatory effects of PFOA on the Bax: Bcl2 ratio and reduced the PFOA-induced gene expression of TNF-α, IL-6, NF-ƙB, and JNK. Conclusion: These findings suggest rutin as a protective agent for PFOA-induced liver injury, albeit the protection was partial. Possible mechanisms are inhibition of oxidative stress, mitochondrial dysfunction, and inflammatory response.

Taurine protects against perfluorooctanoic acid-induced hepatotoxicity via inhibition of oxidative stress, inflammatory, and apoptotic pathways.

We are constantly encountering with low doses of chemicals in everyday life rather than toxic doses at a time. So, ongoing low-dose exposures of environmental chemicals commonly encountered are very likely to cause an adverse health effects. Perfluorooctanoic acid (PFOA) is frequently used for production of an array of consumer products and industrial processes. The present study evaluated the underlying mechanisms of PFOA-induced liver damage and also potential protection by taurine. Male Wistar rats were exposed to PFOA alone and in combination with taurine (25, 50, and 100 mg/kg/day) by gavage for 4 weeks. Liver function tests as well as histopathological examinations were studied. Also, oxidative stress markers, mitochondrial function, and nitric oxide (NO) production in liver tissues were measured. In addition, the expression of apoptosis-related genes (caspase-3, Bax, and Bcl-2), inflammation-associated genes (TNF-α, IL-6, NF-B), and c-Jun-N-terminal kinase (JNK) were evaluated. Taurine significantly reversed serum biochemical and histopathological alterations in the liver tissue following exposure to PFOA (10 mg/kg/day). Similarly, taurine alleviated mitochondrial oxidative damage-induced by PFOA in the liver tissue. An increased Bcl2: Bax ratio with decrees in the expression level of caspase-3, and decreased expression of inflammatory markers (TNF-α and IL-6), NF-B, and JNK were also observed following the administration of taurine. These findings suggest a protective role of taurine against PFOA-induced hepatotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis.

Sodium arsenite accelerates D-galactose-induced aging in the testis of the rat: Evidence for mitochondrial oxidative damage, NF-kB, JNK, and apoptosis pathways.

Aging inhibits male reproductive function and can have an impact on fertility. This study elucidated the accelerating role of sodium arsenite (As3+) on D-galactose-induced reproductive aging in male rats. The rats in the study are divided into nine groups. Group I is young control. Group II is naturally aged 24-month-old rats, other animal groups received As3+ (0.5, 1, and 2 mg/kg/day, i.p.) and/or D-galactose (DG) (50 mg/kg/day, i.p.) for 8 weeks. Then, sperm parameters, histopathological manifestations, oxidative stress markers, and gene expression of inflammatory factors (TNF-α, IL-6, and NF-ƙB), apoptosis-related genes (Bcl-2 and Bax), and C-Jun N-terminal kinase (JNK) were evaluated in testis tissue. As3+ (1 and 2 mg/kg) induced significant changes in evaluated factors compared to control group. Co-treatment with DG and As3+ caused morphological changes as well as a significant decrease in sperm motility and count. In DG + As3+ group, histopathological changes were also more obvious. Moreover, as compared to the DG group, co-treated animals exhibited a significant increase in oxidant markers and a decrease in antioxidant levels. Accordingly, DG co-exposure with As3+ markedly enhances the expressions of TNF-α, IL-6, and NF-ƙB compared to DG alone. Likewise, in the testis of rats treated with As3 + plus DG compared to DG alone, there was up-regulation of Bax (pro-apoptotic), down-regulation of Bcl-2 (anti-apoptotic), and elevation of JNK expression. These findings suggest sodium arsenite as an accelerating cause for D-galactose-induced aging process in testis tissue.

Zinc and selenium supplement mitigated valproic acid-induced testis toxicity by modulating the oxidative redox balance in male rats.

Valproic acid (VPA) is widely used antiepileptic agent which is associated with reproductive toxicity via impairment in oxidative redox. Zinc (Zn) and selenium (Se) are trace element with antioxidant effect that known to be essential for spermatogenesis. In the current study, the protective effect of co-administration of Zn and Se on VPA-induced reproductive toxicity in male rats was evaluated. Forty-eight male rats were divided into 8 groups of six (n=6): Control group (treated with normal saline); VPA only (250, 500, 1,000 mg/kg) group; VPA (500 mg/kg) plus Zn (2 mg/kg) group; VPA (500 mg/kg) plus Se (1.5 mg/kg) group; VPA (500 mg/kg) plus a combination of Zn and Se group; and VPA+vitamin E (20 mg/kg) group. The Animals were sacrificed after 28 days of treatment and sperm analysis was taken. Also, evaluation of oxidative stress markers including malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH) and histopathological changes were done on testis tissue. Morphological changes and a significant decrease in motility and sperm count in rats treated with VPA were observed. Also, an increase in oxidative stress marker, including MDA and PC and a decrease in GSH level was evident in VPA group. Zn and Se administration was able to protect against sperm abnormality, ameliorate the histological change in testis tissue, and suppressed the increase in oxidative stress markers induced by VPA. These results indicated that combination therapy with Zn and Se showed better an ameliorative effect than each one alone. Therefore, it can be suggested as an effective supplement for reproductive impairment in VPA-treated patient.

Zinc Deficiency and Oxidative Stress Involved in Valproic Acid Induced Hepatotoxicity: Protection by Zinc and Selenium Supplementation.

Valproic acid (VPA) is an antiepileptic drug, which its usage is limited due to its hepatotoxicity. The present study was conducted to investigate the efficacy of zinc (Zn) and selenium (Se), necessary trace elements, against VPA-induced hepatotoxicity in Wistar rats. The animals were divided into five groups: control, VPA 200 mg/kg, VPA + Zn (100 mg/kg), VPA + Se (100 mg/kg), and VPA + Zn + Se. The administration of VPA for four consecutive weeks resulted in decrease in serum level of Zn in rats. Also, an increase in liver marker enzymes (ALT and AST) and also histological changes in liver tissue were shown after VPA administration. Oxidative stress was evident in VPA group by increased lipid peroxidation (LPO), protein carbonyl (PCO), glutathione (GSH) oxidation, and reducing total antioxidant capacity. Zn and Se (100 mg/kg) administration was able to protect against deterioration in liver enzyme, abrogated the histological change in liver tissue, and suppressed the increase in oxidative stress markers. Zn and combination of Zn plus Se treatment showed more protective effects than Se alone. These results imply that Zn and Se should be suggested as effective supplement products for the prevention of VPA-induced hepatotoxicity.