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<p>Diethyl nitrosamine (DEN) is a potent carcinogen and hepatotoxin that induces multi-organ damage by causing oxidative stress, inflammation, dyslipidemia, and apoptosis. This study investigated the protective efficacy of diphenyl diselenide (DPDS), a synthetic organo-selenium compound, in mitigating DEN-induced hepatorenal toxicity. Experimental rats were treated with corn oil and DPDS (3 and 5&#xa0;mg/kg) orally for 21&#xa0;days, with a single intraperitoneal dose of DEN (200&#xa0;mg/kg) on day 15. Serum and tissue (liver and kidney) were obtained for biochemical and histological examination. Our findings revealed that DEN significantly increased (<i>p</i> &lt; <i>0.05</i>) biomarkers of hepatic and renal injury, namely alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, serum creatinine, urea, and dyslipidemia, in addition to increasing oxido-inflammatory markers (myeloperoxidase, nitric oxide, and xanthine oxidase). Furthermore, DEN reduced (<i>p</i> &lt; <i>0.05</i>) antioxidant activities, including superoxide dismutase, catalase, glutathione peroxidase, and glutathione-<i>s</i>-transferase activities, alongside decreased glutathione and total sulfhydryl levels. The DEN-induced apoptosis was caused by reducing Bcl2 and increasing Bax, Bax/Bcl2 ratio, and p53 levels. DPDS supplementation (3&#xa0;mg/kg or 5&#xa0;mg/kg) markedly attenuated these increases, liver and renal injury, modulated lipid metabolism, improved antioxidant activities, and inhibited oxido-inflammatory and apoptotic effects. The present study data revealed that treatment with DPDS reduces liver and kidney damage, improves endogenous antioxidant activity, and suppresses oxido-inflammatory and apoptotic responses in the liver and kidney, demonstrating an essential protective role during DEN-induced hepatorenal toxicity.</p>

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Diphenyl diselenide promotes antioxidant activity and reduces apoptosis, offering hepatorenal protection in Wistar rats exposed to diethyl nitrosamine

  • 期刊论文

  • 发表日期：

    2025年10月31日

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  • Solomon Owumi,
  • Praise Dyap Emmanuel,
  • Joseph Chimezie,
  • Favour Onyinyechi Joel,
  • Bello Idris,
  • Jesutosin O. Babalola,
  • Olatunde Owoeye

摘要

Diethyl nitrosamine (DEN) is a potent carcinogen and hepatotoxin that induces multi-organ damage by causing oxidative stress, inflammation, dyslipidemia, and apoptosis. This study investigated the protective efficacy of diphenyl diselenide (DPDS), a synthetic organo-selenium compound, in mitigating DEN-induced hepatorenal toxicity. Experimental rats were treated with corn oil and DPDS (3 and 5 mg/kg) orally for 21 days, with a single intraperitoneal dose of DEN (200 mg/kg) on day 15. Serum and tissue (liver and kidney) were obtained for biochemical and histological examination. Our findings revealed that DEN significantly increased (p < 0.05) biomarkers of hepatic and renal injury, namely alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, serum creatinine, urea, and dyslipidemia, in addition to increasing oxido-inflammatory markers (myeloperoxidase, nitric oxide, and xanthine oxidase). Furthermore, DEN reduced (p < 0.05) antioxidant activities, including superoxide dismutase, catalase, glutathione peroxidase, and glutathione-s-transferase activities, alongside decreased glutathione and total sulfhydryl levels. The DEN-induced apoptosis was caused by reducing Bcl2 and increasing Bax, Bax/Bcl2 ratio, and p53 levels. DPDS supplementation (3 mg/kg or 5 mg/kg) markedly attenuated these increases, liver and renal injury, modulated lipid metabolism, improved antioxidant activities, and inhibited oxido-inflammatory and apoptotic effects. The present study data revealed that treatment with DPDS reduces liver and kidney damage, improves endogenous antioxidant activity, and suppresses oxido-inflammatory and apoptotic responses in the liver and kidney, demonstrating an essential protective role during DEN-induced hepatorenal toxicity.