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Background <p>This research aimed to explore if carnitine (CARN) deficiency is a risk factor in methotrexate (MTX)-mediated acute kidney injury (AKI) and to mechanistically reveal the potential attenuating effect of CARN against MTX-mediated nephrotoxicity.</p> Methods <p>Thirty-six adult male Wister albino rats were subgrouped into six groups. Groups 1, 2, and 3 received 0.9% normal saline (0.5 mL/200 g, i.p.), mildronate (MD, 200&#xa0;mg/kg/day, i.p.), and <span>l</span>-carnitine (CARN, 200&#xa0;mg/kg/day, i.p.) for 10 uninterrupted days, respectively. Groups 4, 5, and 6 received similar doses of normal saline, MD, and CARN for 5 days prior to as well as following a solo dose of methotrexate (MTX, 20&#xa0;mg/kg, i.p.), respectively.</p> Results <p>Treatment with a single dose of MTX significantly boosted serum nephrotoxicity as well as hepatotoxicity indices; additionally, it increased the percentage of collagen deposition in rat kidney tissues with obvious histopathological changes. Moreover, MTX lowered kidney levels of adenosine triphosphate (ATP) and amplified acetyl-CoA carboxylase-1 (ACC-1) in kidney tissues. In MD-treated rats, MTX progressively boosted nephrotoxicity indices and collagen disposition in kidney tissues as well as progressive additional reduction in ATP as compared with MTX-treated rats and serum carnitine levels compared with MD-treated rats. Carnitine administration totally counteracted the biochemical and histopathological alterations mediated by MTX to the normal measures.</p> Conclusions <p>This research proposes that carnitine deficiency is a potential risk factor in the development of MTX-mediated AKI. MTX disrupts ACC1 signaling with the consequential inhibition of ATP production. Carnitine supplementation attenuates MTX-mediated AKI. Our results are preliminary and mandate further mechanistic study to justify the progression of AKI by MTX in CARN-deficient rats.</p>

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Carnitine deficiency augments methotrexate-mediated acute renal injury in rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月26日

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  • Fatema Alaa El-Din Selim,
  • Mahmoud M. Khattab,
  • Abdel-Moneim M. Osman,
  • Riham M. Karkeet,
  • Mervat M. Omran,
  • Marwa Sharaky,
  • Mohamed M. Sayed-Ahmed

摘要

Background

This research aimed to explore if carnitine (CARN) deficiency is a risk factor in methotrexate (MTX)-mediated acute kidney injury (AKI) and to mechanistically reveal the potential attenuating effect of CARN against MTX-mediated nephrotoxicity.

Methods

Thirty-six adult male Wister albino rats were subgrouped into six groups. Groups 1, 2, and 3 received 0.9% normal saline (0.5 mL/200 g, i.p.), mildronate (MD, 200 mg/kg/day, i.p.), and l-carnitine (CARN, 200 mg/kg/day, i.p.) for 10 uninterrupted days, respectively. Groups 4, 5, and 6 received similar doses of normal saline, MD, and CARN for 5 days prior to as well as following a solo dose of methotrexate (MTX, 20 mg/kg, i.p.), respectively.

Results

Treatment with a single dose of MTX significantly boosted serum nephrotoxicity as well as hepatotoxicity indices; additionally, it increased the percentage of collagen deposition in rat kidney tissues with obvious histopathological changes. Moreover, MTX lowered kidney levels of adenosine triphosphate (ATP) and amplified acetyl-CoA carboxylase-1 (ACC-1) in kidney tissues. In MD-treated rats, MTX progressively boosted nephrotoxicity indices and collagen disposition in kidney tissues as well as progressive additional reduction in ATP as compared with MTX-treated rats and serum carnitine levels compared with MD-treated rats. Carnitine administration totally counteracted the biochemical and histopathological alterations mediated by MTX to the normal measures.

Conclusions

This research proposes that carnitine deficiency is a potential risk factor in the development of MTX-mediated AKI. MTX disrupts ACC1 signaling with the consequential inhibition of ATP production. Carnitine supplementation attenuates MTX-mediated AKI. Our results are preliminary and mandate further mechanistic study to justify the progression of AKI by MTX in CARN-deficient rats.