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Purpose <p>Paracetamol (PCM) is a widely used analgesic and antipyretic; however, prolonged or excessive exposure is associated with nephrotoxicity mediated by oxidative stress and renal tubular injury. Despite the availability of interventions such as N-acetylcysteine in acute paracetamol toxicity, effective and targeted therapies for paracetamol-induced nephrotoxicity remain inadequate, leading to increased investigation of herbal-based therapeutic options. The present study investigated the nephroprotective potential of the hydroalcoholic extract of <i>Rhus succedanea</i> Linn. whole plant (RSE) against PCM-induced nephrotoxicity using integrated in vitro and in vivo approaches.</p> Methods <p>Cytotoxicity and cytoprotective effects of RSE were initially assessed in HEK293 cells using the MTT assay. For in vivo evaluation, sixty male Wistar rats were divided into ten groups (<i>n</i> = 6). Nephrotoxicity was induced by administering PCM (200&#xa0;mg/kg, intraperitoneally) for 14 days. RSE was administered orally at doses of 200, 400, and 800&#xa0;mg/kg under preventive and curative regimens, while silymarin (100&#xa0;mg/kg, p.o.) served as the standard reference drug. Preventive treatment was given concomitantly with PCM, whereas curative treatment commenced after PCM exposure. Renal function was assessed through physiological parameters, urine output, serum biochemical markers, electrolyte balance, oxidative stress biomarkers (SOD, CAT, GSH, and MDA), and histopathological examination of renal tissues.</p> Results <p>PCM administration caused marked renal dysfunction, oxidative stress, and histological damage. Treatment with RSE significantly and dose-dependently ameliorated PCM-induced alterations, with the highest dose (800&#xa0;mg/kg) exhibiting nephroprotective effects comparable to silymarin in both regimens.</p> Conclusion <p>These findings suggest that <i>Rhus succedanea</i> possesses significant nephroprotective activity, likely mediated through antioxidant mechanisms, supporting its potential as a phytotherapeutic candidate for managing drug-induced nephrotoxicity.</p>

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Integrated in Vitro and in Vivo Assessment of Rhus succedanea for Protection against Paracetamol-Induced Nephrotoxicity

  • 期刊论文

  • 发表日期：

    2026年2月9日

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  • Rohini Pujari,
  • Aishwarya Dange

摘要

Purpose

Paracetamol (PCM) is a widely used analgesic and antipyretic; however, prolonged or excessive exposure is associated with nephrotoxicity mediated by oxidative stress and renal tubular injury. Despite the availability of interventions such as N-acetylcysteine in acute paracetamol toxicity, effective and targeted therapies for paracetamol-induced nephrotoxicity remain inadequate, leading to increased investigation of herbal-based therapeutic options. The present study investigated the nephroprotective potential of the hydroalcoholic extract of Rhus succedanea Linn. whole plant (RSE) against PCM-induced nephrotoxicity using integrated in vitro and in vivo approaches.

Methods

Cytotoxicity and cytoprotective effects of RSE were initially assessed in HEK293 cells using the MTT assay. For in vivo evaluation, sixty male Wistar rats were divided into ten groups (n = 6). Nephrotoxicity was induced by administering PCM (200 mg/kg, intraperitoneally) for 14 days. RSE was administered orally at doses of 200, 400, and 800 mg/kg under preventive and curative regimens, while silymarin (100 mg/kg, p.o.) served as the standard reference drug. Preventive treatment was given concomitantly with PCM, whereas curative treatment commenced after PCM exposure. Renal function was assessed through physiological parameters, urine output, serum biochemical markers, electrolyte balance, oxidative stress biomarkers (SOD, CAT, GSH, and MDA), and histopathological examination of renal tissues.

Results

PCM administration caused marked renal dysfunction, oxidative stress, and histological damage. Treatment with RSE significantly and dose-dependently ameliorated PCM-induced alterations, with the highest dose (800 mg/kg) exhibiting nephroprotective effects comparable to silymarin in both regimens.

Conclusion

These findings suggest that Rhus succedanea possesses significant nephroprotective activity, likely mediated through antioxidant mechanisms, supporting its potential as a phytotherapeutic candidate for managing drug-induced nephrotoxicity.