Shilajit potentiates the effect of chemotherapeutic drugs and mitigates metastasis induced liver and kidney damages in osteosarcoma rats

Abstract

Osteosarcoma is a primary malignant cancer of the bone identified by the direct formation of osteoid tissue or immature bone by cancer cells. The liver and kidneys represent two major secondary organs to which osteosarcoma metastasizes. In this study, we assessed Shilajit, a phytomineral diffusion traditionally used in Ayurvedic medicine, for its possible protective effects against metastasis induced liver and kidney damages in an osteosarcoma rat model. Osteosarcoma rats displayed typical dysregulation of serum levels of hepatic and renal functional markers (p < 0.05) including aspartate aminotransferase (AST)* and alanine aminotransferase (ALT), alkaline phosphatase (ALP), total proteins, albumin, bilirubin, creatinine, urea, and uric acid. Changes in functional markers were also positively correlated with marked histopathological alterations in liver and kidney tissues. Whereas Shilajit's treatment of osteosarcoma rates in combination with CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy drug cocktail significantly (p < 0.05) reversed the studied functional markers to their near-normal levels. Co-treatment of shilajit and drug cocktails also markedly alleviated histopathological changes in liver and kidney tissues. Correlation co-efficient analysis of hepatic and renal functional markers revealed a significant inter-association among these markers. Collectively, present data indicate that shilajit may potentiate the effects of chemotherapy drugs and mitigate the metastasis-induced liver and kidney damage in osteosarcoma. Thus, the findings of this study substantiate the beneficial health effects of shilajit and promote its regular consumption.

Keywords: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CMF, cyclophosphamide, methotrexate and 5, fluorouracil; HDS, high dose shilajit; Histology; Kidney; LDS, low dose shilajit; Liver; Metastasis; OS, osteosarcoma; Osteosarcoma; Shilajit.

Fig. 1

H&E stained liver tissue sections from control (A), OS (B), OS + CMF (C), OS + CMF + LDS (D), OS + CMF + HDS (E) rats. Histology of osteosarcoma rats (OS group) displaying ballooning degeneration of hepatocytes (indicated by triangle), sinusoid congestion (indicated by hallow arrow) and inflammation (arrow) as against normal histology seen in the control group. Tissue sections from OS + CMF groups showed regeneration of hepatocytes but lesser sinusoid congestion and moderate inflammation, Rats from OS + CMF + LDS group demonstrated reduced degeneration, no sinusoid congestion and mild inflammation in liver tissues, whereas near normal histology was observed in tissue sections from OS + CMF + HDS group rats.

Fig. 2

H&E stained kidney tissue sections from control (A), OS (B), OS + CMF (C), OS + CMF + LDS (D), OS + CMF + HDS (E) rats. Histology of osteosarcoma rats (OS group) displaying shrinking of glomerular tuft (arrow) and tubular atrophy (hallow arrow) as compared to normal histology seen in the control group. Tissue sections from OS + CMF groups showed slightly congested glomeruli and moderate tubular atrophy. Rats from OS + CMF + LDS group demonstrated no glomeruli congestion and mild tubular atrophy, whereas no apparent histological changes were noted in kidney tissue sections from OS + CMF + HDS group rats.