Effect of Some Anticancer Drugs and Combined Chemotherapy on Renal Toxicity

Abstract

The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX+5-FU+CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX+5-FU+CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU+CY administered jointly is lower than in monotherapy.

Evaluation of the Cytotoxic Effects of CAM Therapies: AnIn VitroStudy in Normal Kidney Cell Lines

“…Increase in levels of malondialdehyde along with decreased levels of glutathione concentrations, after treatment with 5-FU, was also seen in renal tissues [5]. Similar results were observed in another study that showed 5-FU-induced nephrotoxicity in normal rats [6]. …”

“…However, this killing is nonselective and not only eliminates the fast-growing cancer cells but also other fast-growing cells in the body, including hair and blood cells, owing to which it exhibits severe toxicity and undesirable side effects [4]. 5-FU has been shown to be associated with renal toxicity [5, 6]. This puts the patient at added risk when undergoing chemotherapy.…”

Effects of quercetin on methotrexate-induced nephrotoxicity in rats

“…The experimental studies suggest that morphological changes in tubular and glomerular area after Mtx treatment. 29 Histopathological evidence of kidney injury includes degenerated and vacuolated tubules, tubular atrophy or necrosis, changes in Bowman’s space, vascular congestion, and glomerular fibrosis. At the same time, owing to the deterioration in the balance of oxidant–antioxidant mechanisms and shifting toward the oxidant status, changes in the levels of enzymes SOD and MDA can be observed.…”

Taurine ameliorates 5-flourouracil-induced intestinal mucositis, hepatorenal and reproductive organ damage in Wistar rats

“…Previous findings also reveal that 5-FU causes male reproductive organ damage by inhibiting thymidylate synthetase and by incorporation into genetic material. 11,[47][48][49] Histological analysis indicate that Tau administration attenuated the 5-FU-induced degeneration of seminiferous epithelium, vacuolization of Sertoli cells in testis and atrophy of prostatic acini, nuclear stratification, and increased secretion in prostate.…”