Alleviation of cisplatin-induced hepatotoxicity and nephrotoxicity by L-carnitine

Abstract

Objectives: To assess the protective effect of L-carnitine in reducing cisplatin toxicity via estimating biochemical tests, histomorphometric, and immunohistochemistry (IHC) of β-catenin and cyclin D.

Materials and methods: Fifteen adult male rabbits were used in this study and allocated into 3 groups; Group 1 (Control negative), rabbits of this group were not given any treatment. In group 2, the animals were injected with cisplatin single-dose/per week. Group 3 rabbits were treated with Cisplatin+L-carnitine orally by gavage tube for 29 days. At the end of the experiments, blood samples from all rabbits were taken from the earlobe, and then the biochemical test was done, the kidney and tissue sections were prepared for both H& E and IHC for both β-catenin and cyclin D genes.

Results: Treatment with L-carnitine reduced the injury effect of cisplatin via a decline in serum creatinine, urea, bilirubin, GPT, GOP, and ALP significantly (P<0.05). Also, administration of LC attenuates the histopathologic abnormality in the kidney (15.71% vs 85.18%) and liver (score 3 vs 15 ) induced by cisplatin. L-carnitine elevates the expression of β-catenin and cyclin D in renal and hepatic parenchyma by diffuse, moderate-strong positivity vs cisplatin that showed local-weak staining.

Conclusion: These findings imply that L-carnitine, by its pleiotropic actions in activating Wnt signaling, alleviates cisplatin-induced renal and hepatic destruction. It might be a method of preventing cisplatin-related nephrotoxicity and hepatotoxicity.

Keywords: Cisplatin; Cyclin D; Hepatic regeneration; L-carnitine; Tubular necrosis; β-catenin.

Figure 1

Microscopic features of kidney section showed

Figure 2

Column chart showing; A: Percentages for each kidney lesion in control negative, cisplatin, and L-carnitine groups. B: Scores for the liver parenchyma’s lesions in all groups. Scores with different alphabetical letter superscripts are significantly different (P<0.05)

Figure 3

Microscopic features of a liver section showed;

Figure 4

Photomicrograph of β-catenin cytoplasmic immunostaining from all examined groups

Figure 5

Photomicrograph of cyclin D1 cytoplasmic immunostaining from both groups. A: Focal-weak staining (score 2) in the kidney section of the cisplatin group. B: Diffuse moderate-strong staining (score 9) in the kidney section of the L-carnitine group. C: Focal-weak staining (score 2) in a liver section of the cisplatin group. D: Diffuse moderate-strong staining (score 16) in the liver section of the L-carnitine group