Farnesol attenuates cadmium-induced kidney injury by mitigating oxidative stress, inflammation and necroptosis and upregulating cytoglobin and PPARγ in rats

Alruhaimi, Reem S ORCID: https://orcid.org/0000-0003-3746-8582, Hassanein, Emad H M ORCID: https://orcid.org/0000-0003-4865-2342, Ahmeda, Ahmad F, Atwa, Ahmed M ORCID: https://orcid.org/0000-0001-8580-4179, Alnasser, Sulaiman M, Sayed, Ghadir A, Alotaibi, Meshal, Alzoghaibi, Mohammed A and Mahmoud, Ayman M ORCID: https://orcid.org/0000-0003-0279-6500 (2024) Farnesol attenuates cadmium-induced kidney injury by mitigating oxidative stress, inflammation and necroptosis and upregulating cytoglobin and PPARγ in rats. Tissue and Cell, 90. 102526. ISSN 0040-8166

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Abstract

Heavy metals are environmental pollutants that can harm animals and humans even at low concentrations. Cadmium (Cd) is known for its serious health effects on different organs and its toxicity is associated with oxidative stress (OS) and inflammation. Farnesol (FAR), a sesquiterpene alcohol found in many vegetables and fruits, possesses promising anti-inflammatory and antioxidant activities. This study evaluated the effect of FAR on Cd-induced kidney injury, pinpointing its effect of the redox status, inflammation, fibrosis and necroptosis. Rats in this study received FAR for 14 days and Cd on day 7. Elevated serum creatinine, urea and uric acid, and several kidney histopathological alterations were observed in Cd-administered rats. Cd increased MDA, decreased antioxidants, downregulated PPARγ and upregulated NF-κB p65, IL-6, TNF-α, and IL-1β. Necroptosis mediators (RIP1, RIP3, MLKL, and caspase-8) and α-SMA were upregulated, and collagen deposition was increased in Cd-administered rats. FAR ameliorated kidney injury markers and tissue damage, attenuated OS, suppressed NF-κB and inflammatory mediators, and enhanced antioxidants. In addition, FAR suppressed RIP1, RIP3, MLKL, caspase-8, and α-SMA, and enhanced kidney cytoglobin and PPARγ. In conclusion, FAR protects against Cd nephrotoxicity by suppressing OS, inflammatory response and necroptosis, effects associated with enhanced antioxidants, cytoglobin, and PPARγ.