Cisplatin induced testicular damage through mitochondria mediated apoptosis, inflammation and oxidative stress in rats: impact of resveratrol

Abstract

The target of this study was to explore the role of mitochondria mediated apoptosis and inflammation in cisplatininduced testicular damage and to evaluate the ameliorative effect of resveratrol. Adult male Wistar rats were randomly allocated to 4 groups. Group I (Control) received normal saline, Group II (Resveratrol) received resveratrol (50 mg/kg/day), Group III (Cisplatin) received cisplatin (7.5 mg/kg/week, i.p.) and Group IV (Resveratrol + Cisplatin) received resveratrol and cisplatin in the same regimen of treatment. Treatment with resveratrol in Groups II and IV started 48h before cisplatin injection and continued for further 4 successive weeks. Cisplatin-treated rats showed reduced body weight, absolute testes weight and sperm count, motility and viability. On the other hand, cisplatin treatment increased the percentage of sperm abnormalities. It also decreased serum testosterone level, mitochondrial membrane potential while, increased cytochrome C liberation from the mitochondria into the cytosol. The activities of caspase-3 &-9 were increased. The level of TNF-α, IL-6 and Bax were increased whereas Bcl-2 was decreased. Oxidative stress markers were found to increase with a concomitant reduction in the antioxidant enzymes and GSH levels. These results were confirmed by immunohistochemical and histopathological analysis. Contrary to all these results, there were improvements in cisplatin induced testicular damage through attenuation of mitochondria mediated apoptosis, inflammation, and oxidative stress owing to resveratrol pretreatment. Thus, resveratrol, as a potential therapeutic agent, may hold promise in preventing mitochondria mediated apoptosis and inflammation in cisplatin-induced testicular damage in rats.

Evaluation of protective effects of gallic acid on cisplatin‐induced testicular and epididymal damage

“…Similarly, Aly and Eid (2020) have reported that CP treatment (a single dose of 7.5 mg/kg) increased the activity of Caspase-3 and Bax, while decreased the activity of Bcl-2 in testis. They also showed that resveratrol decreased the activity of Caspase-3 and Bax, but increased the activity of Bcl-2.…”

“…Previous studies have reported that CP (a single dose of 6 mg/kg and 7 mg/kg) causes upregulation of Caspase‐3 and downregulation of Bcl‐2 (Kohsaka et al., 2020; Nna et al., 2020). Similarly, Aly and Eid (2020) have reported that CP treatment (a single dose of 7.5 mg/kg) increased the activity of Caspase‐3 and Bax, while decreased the activity of Bcl‐2 in testis. They also showed that resveratrol decreased the activity of Caspase‐3 and Bax, but increased the activity of Bcl‐2.…”

A Flavonoid-Rich Extract from Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, Shows Protective Effects in a Murine Model of Cadmium-Induced Testicular Injury

“…The adverse effect on body weight could be probably correlated to its harmfulness on many body systems, and the mechanism may be linked to the generation of free radicals [ 51 ]. With regard to the weight of the testis, it is mainly dependent on the germinal epithelium and the number of germ cells [ 52 , 53 , 54 ]. The significant decline demonstrated after CdCl 2 challenge can be considered an important parameter of toxicity and it may be due to the histopathological damages in the seminiferous tubules (reduced MSTD and Johnsen’s score).…”

“…Other studies have demonstrated the protective and therapeutic effects of other substances against different toxics in testes. In particular, Re showed a protective action against testicular toxicity as it upregulated Bcl2, downregulated p53 and Bax gene expression [ 20 , 54 ], and reduced inflammatory cascade [ 54 ]. Furthermore, marked improvements in sperm parameters and histopathological damages were observed in the Re-pretreated mice [ 34 ].…”

Achillea millefolium alleviates testicular damage in paclitaxel‐intoxicated rats via attenuation of testicular oxido‐inflammatory stress and apoptotic responses

“…According to our results, while paclitaxel significantly increased TNFα, IL-1β and NFκB levels, AM significantly decreased the levels of inflammatory parameters at a dose of 400 mg/kg. In toxicity studies conducted with various chemotherapeutic agents, inflammatory parameters have been shown to increase in testicular tissue (Aly & Eid, 2020;Sherif et al, 2014). To our knowledge, this is the first study to prove a,b,c Differences between the groups (p < 0.05).…”