Candesartan in a rat model of testicular toxicity: New insight on its protective mechanism

Abstract

Cisplatin (CDDP) is widely used as an effective chemotherapy; nevertheless, its use is associated with male reproductive system damage. Candesartan (Cand) is an angiotensin II receptor blocker which showed a protective effect against CDDP-induced testicular toxicity. This study was implemented to investigate further novel molecular protective effect of Cand. Animals were divided into four groups and treated for 10 days as: Group I (Normal control): received saline, Group II (Cand control): treated with Cand (10 mg/kg/day) orally, Group III (CDDP): injected with a single dose of 10 mg/kg CDDP intraperitoneally (ip), Group IV (Cand + CDDP): treated with Cand (10 mg/kg/day) orally plus a single ip dose of 10 mg/kg CDDP at day 3. Blood and testicular tissue collections were done at the end of the experiment. A marked decrease in testicular, body, and relative body weights in addition to testosterone level was observed in the CDDP group when compared with normal rats. In addition, exposure to CDDP showed a marked upregulation of testicular TNF-α mRNA level and a significant rise in testicular levels of total oxidant status, oxidative stress index (OSI) ratio, pro-apoptotic protein Bax, Bax/Bcl-2 ratio alongside with a marked reduction in testicular levels of total antioxidant status, antiapoptotic protein Bcl-2, and a significant upregulation of the testicular caspase-3 expression in comparison to normal group. Histopathological findings after CDDP injection showed apoptosis and necrosis in testicular tissues. Administration of Cand ameliorated these biochemical and histopathological findings. Cand exhibited a novel protective mechanism against CDDP induced-gonadal damage via antioxidant, anti-inflammatory, and anti-apoptotic activities. Impact statement Cisplatin is a commonly used drug in the treatment of solid tumors and its application is associated with testicular toxicity. The effect of candesartan in cisplatin-induced testicular toxicity and its fundamental mechanism of action were investigated. Candesartan had certainly repaired the testicular injury and ameliorated both biochemical and histopathological changes. Candesartan mitigated the gonadotoxicity induced by cisplatin via antioxidative, anti-inflammatory, and antiapoptotic actions.

RETRACTED ARTICLE: Candesartan Protects Against Cadmium-Induced Hepatorenal Syndrome by Affecting Nrf2, NF-κB, Bax/Bcl-2/Cyt-C, and Ang II/Ang 1–7 Signals

“…At the same time, it decreased the expression of the pro-apoptotic Bax and Cyt-C. These findings are consistent with previous studies that found candesartan could attenuate apoptosis via modulating apoptotic and anti-apoptotic proteins [ 49 , 57 ].…”

“…In contrast, candesartan administration remarkably restored the antioxidant balance. Sherif and Sarhan [ 49 ] reported that candesartan antagonizes the oxidative stress damage elicited by Ang II in cisplatin-induced testicular damage. Furthermore, we found that Cd toxicity caused a marked decrease in Nrf2 levels in hepatic and renal tissues.…”

The effect of Sambucus nigra fruit extract in three chemotropic cycles of cisplatin drug on male reproductive system of mice

“…Our results illustrated that cisplatin greatly reduced body weight. These results were consistent with the reports made (30,31). As we know, a lot of chemotherapy drugs such as cisplatin can in uence the digestive system like nausea, vomiting and diarrhea.…”

“…These results weren't consistent with the results of the work of Azarbarz et al (33). Decreased TSI occurs following a decrease in testicular mass that can occur due to suppression of spermatogenic function in the testes and atrophy of seminiferous tubules by cisplatin administration (30,31,34). This improvement in TSI and body weight in different SNA-treated groups can be attributed to the results of studies on satiety hormones such as leptin, which can increase appetite and overeating (35).…”

d‐ribose‐l‐cysteine abrogates testicular maladaptive responses induced by polychlorinated bisphenol intoxication in rats via activation of the mTOR signaling pathway mediating inhibition of apoptosis, inflammation, and oxidonitrergic flux

“…A total of 300 spermatozoa were examined on each slide (3000 cells in each group), and the head, tail, and total abnormality rates of spermatozoa were expressed as percentages as previously explained. [ 31 ]…”