The molecular and biochemical insight view of grape seed proanthocyanidins in ameliorating cadmium-induced testes-toxicity in rat model: implication of PI3K/Akt/Nrf-2 signaling.

The present study aims to evaluate the protective effect of grape seed proanthocyanidins (GSP) on cadmium (Cd)-induced testicular apoptosis, inflammation, and oxidative stress in rats. A total of 24 male Wistar rats were divided into four groups, namely control, GSP (100 mg/kg BW), Cd (5 mg/kg BW), and Cd+GSP. Cd-treated rat testes exhibited a significant increment in oxidative stress mediated inflammation and apoptosis. Pre-administration of GSP exhibit significant protection against the apoptotic and inflammatory damages elicited by Cd and uphold the intercellular antioxidant status in testes. Histological changes were studied and the immunohistochemical staining for caspase 3, HSP70, and eNOS protein expressions were also analyzed to justify the protective action of GSP. Furthermore, GSP prevented DNA damage, and enhanced the expression of antioxidant responsive elements Nrf2/HO-1 by PI3K/Akt-dependent pathway. Therefore, our results suggest that GSP acts as a multipotent antioxidant entity against Cd-induced oxidative testicular toxicity in rats.

Neuroprotective efficacy of hesperetin against cadmium induced oxidative stress in the brain of rats.

The present study was designed to investigate the neuroprotective effect of hesperetin (Hp) against cadmium (Cd)-induced neurotoxicity in rats. Cadmium (3 mg/kg body weight (b.w.), subcutaneous) administration for 3 weeks demonstrated neurotoxicity in rats by the decreased activity of acetylcholinesterase in the brain. The oxidative stress markers (thiobarbituric acid reactive substances and protein carbonyls) were significantly increased with decreased enzymatic (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase) and non-enzymatic antioxidants (reduced glutathione, total sulphydryl groups and vitamin C). The proteolytic and membrane-bound enzymes (Na+ K+-ATPase, Mg2+-ATPase and Ca2+-ATPase) were also decreased with increased apoptotic markers (Bcl2 Associated X Protein (Bax), cytochrome C, caspase 3 and 9) and decreased anti-apoptotic marker (B-cell lymphoma 2 (Bcl2)) in the brain of Cd-treated rats. Moreover, Cd administration significantly decreased the mitochondrial electron transport chain complexes (I, II, III and IV) in the brain of rats. Preadministration of Hp (40 mg/kg b.w., oral) significantly attenuated the Cd-induced oxidative stress and mitochondrial dysfunction, restored the antioxidant and membrane-bound enzyme activities and decreased apoptosis in the brain of rats.

Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats.

The present study was to evaluate the hepatoprotective effect of hesperetin (HTN) on cadmium (Cd) induced hepatotoxicity in male Wistar rats. Administration of Cd (3 mg/kg body weight/day) subcutaneously for 21 days, the levels of hepatic markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and bilirubin were significantly increased in serum. The levels oxidative stress markers, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), conjugated dienes (CD) and protein carbonyl content (PCC) were also significantly increased while the levels of vitamin C, vitamin E, reduced glutathione (GSH), total sulphydryl group (TSH) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) were significantly decreased in the liver of Cd intoxicated rats. HTN, a flavanone in citrus fruits, administrated orally along with Cd injection for 21 days, significantly revert back the status of serum hepatic markers, oxidative stress markers and antioxidant markers in the liver tissue to near normal level in a dose dependent manner. HTN at a dose of 40 mg/kg body weight/day exhibits significant (p<0.05) hepatoprotection compared with other two doses (10 and 20 mg/kg body weight/day). The histopathological studies in the liver of rats also supported that HTN (40 mg/kg) markedly reduced the toxicity of Cd and preserved the histoarchitecture of the liver tissue to near normal. Thus, the results suggest that HTN acts as a potent hepatoprotective agent against Cd induced hepatotoxicity in rats.

Hesperetin, a citrus flavonone, protects potentially cadmium induced oxidative testicular dysfunction in rats.

The present study was aimed to evaluate the protective effect of hesperetin (Hp) on cadmium (Cd) induced oxidative testicular toxicity in rats. Subcutaneous administration of Cd (3mg/kg body weight) for 21 days significantly elevated the levels of oxidative stress markers, Cd concentration in testis and lowered the levels of enzymatic, non-enzymatic antioxidants and membrane bound enzymes in the testicular tissue. Hp administrated orally along with Cd injection for 21 days, significantly revert back the status of oxidative stress markers, Cd concentration in testis, improved status of antioxidant markers and membrane bound enzymes in the testis to near normal level. The histopathological studies in the testis of rats also supported that Hp (40 mg/kg) markedly reduced the toxicity of Cd and preserved the normal histoarchitecture pattern of the testis. Thus, the results suggest that Hp acts as a potent antioxidative agent against Cd induced testicular toxicity in rats.

Naringenin in combination with vitamins C and E potentially protects oxidative stress-mediated hepatic injury in cadmium-intoxicated rats.

UNLABELLED: Cadmium (Cd)-induced oxidative stress and hepatic injury is one of the major outcomes of chronic Cd toxicity, which can be ameliorated by numerous antioxidants. The present study was undertaken to find the therapeutic efficacy of naringenin (NGN) plus vitamins C and E on Cd-induced oxidative hepatotoxicity in Wistar rats. It has been noticed that Cd intoxication significantly elevates the levels of serum hepatic marker enzymes such as alanine amino transferase, aspartate amino transferase, alkaline phosphatase, lactate dehydrogenase, γ glutamyl transferase, total bilirubin, and hepatic thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes and protein carbonyls. In addition, Cd also decreases the activities of hepatic enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase and the levels of non-enzymatic antioxidants total sulphydryl groups, reduced glutathione, vitamins C and E and histopathological changes in liver. Treatment with NGN and vitamins C and E in combination more significantly improved the altered biochemical and histopathological changes in the liver of Cd-intoxicated rats than the NGN or vitamins C and E treatment alone. CONCLUSION: The present data suggest that combined administration of NGN with vitamins C and E proved to be more beneficial in the treatment of Cd-hepatotoxicity than NGN treatment alone.