Effect of L-carnitine on potassium dichromate-induced nephrotoxicity in rats: modulation of PI3K/AKT signaling pathway

Abstract

Background and purpose: Kidney diseases impose significant global health challenges. Potassium dichromate (PD) is a heavy metal frequently associated with nephrotoxicity. PD prompts oxidative and inflammatory injuries in renal tissues. L-carnitine is a naturally-occurring amino acid commonly used as a supplement. Experimental approach: Forty rats were randomly allocated into 5 groups. Group 1 (normal) received only saline. Nephrotoxicity was induced in the remaining groups by PD (15 mg/kg; i.p). Group 2 served as a nephrotoxic group. Groups 3-5 received L-carnitine (25, 50, and 100 mg/kg; p.o.), respectively for 4 weeks. Findings/Results: PD administration resulted in elevated serum creatinine and blood urea nitrogen accompanied by diminished reduced glutathione and elevated malondialdehyde, tumor necrosis factor-alpha, and transforming growth factor-beta renal tissue contents relative to normal rats. PD also produced apoptotic histopathological injuries and down-regulated PI3K/Akt signaling pathway; signifying ongoing apoptosis. In the current work, L-carnitine use in the selected dose levels resulted in improvement of all the aforementioned serum, renal tissue, and histological parameters relative to nephrotoxic rats. L-carnitine up-regulated PI3K/Akt signaling pathway that was down-regulated post PD use. Conclusion and implications: Collectively, the study highlighted that the possible mechanisms beyond the beneficial effects of L-carnitine are mainly through its antioxidant as well as anti-inflammatory actions. L- carnitine significantly abrogated apoptosis via up-regulation of PI3K/Akt signaling pathway and signified restoration of normal renal cell proliferation and functionality.

Protective Action Mechanisms of Launaea mucronata Extract and Its Nano-Formulation against Nephrotoxicity in Rats as Revealed via Biochemical, Histopathological, and UPLC-QTOF–MS/MS Analyses

“…The renal cortex had enlarged renal corpuscles with a wide renal space, tubular degeneration, and proximal convoluted tubules which displayed vacuolar degeneration with a luminal cast, and distal convoluted tubules which showed the complete loss in the cytoplasmic content with the sloughing of the lining cuboidal cells into the tubular lumen. These findings are in accordance with previous reports [ 65 , 66 , 67 ], which were suggestive that K 2 Cr 2 O 7 -induced toxicity and the induction of oxidative stress and apoptosis arise through the generation of reactive oxygen species (ROS). Consequently, ROS triggered K 2 Cr 2 O 7 toxicity owing to the reduction of hexavalent chromium to the trivalent form, thereby inducing damage to the cellular components [ 68 ].…”

L‐carnitine reverses methotrexate‐induced nephrotoxicity in experimental rat model: Insight on SIRT1/PGC‐1α/Nrf2/HO‐1 axis

“…Lipid peroxidation is indicated by excessive production of MDA (Su et al, 2019). When combined with MTX, LC markedly reduced MDA and enhanced SOD activity, which confirms the antioxidant role of LC in ameliorating the toxic effects of drug-induced nephrotoxicity (Koohpeyma et al, 2021b;Salama et al, 2022;Sener et al, 2006). TNF-α and IL-6 are inflammatory cytokines that contribute to systemic as well as local renal cell inflammation.…”

Combined β-Sitosterol and Trimetazidine mitigate potassium dichromate-induced cardiotoxicity in rats through the interplay between NF-κB/AMPK/mTOR/TLR4 and HO-1/NADPH signaling pathways

“…It is a xenobiotic agent and a heavy metal that is linked to multiple organ toxicity. Many cellular metabolites reduce PD to produce chromium, leading to the overproduction of reactive oxygen species (Salama et al, 2022). The overproduction of free radicals is thought to be linked to its toxicity by causing oxidative damage to the tissues of the liver, brain, heart, and kidneys.…”