Abstract
Introduction: Most anticancer therapies are seldom effective by single anticancer drug due to biologic heterogeneity and multiple genetic alterations stimulating the use of anticancer drug combinations. Methotrexate/cisplatin (MTX/CPT) has shown beneficial effects in the treatment of metastatic and malignant tumors, but its use may perturb kidney function. Objectives: The present study assessed the protective effects of melatonin (MT) and alpha-lipoic acid (ALA) against kidney toxicity induced by MTX/CPT in albino rats. Materials and Methods: Forty-eight adult male albino rats were randomized into groups and pretreated with MT (10 mg/kg), ALA (10 mg/kg) and MT+ALA daily for five days before treatment with 20 mg/kg of MTX and 5 mg/kg of CPT intraperitoneally on the fifth day. After overnight fast, rats were sacrificed, serum samples were centrifuged from blood samples and assessed for renal function parameters and electrolytes. Kidneys were assessed for oxidative stress (OS) markers and pathology. Results: Significant (P<0.001) increases in serum creatinine, urea, and uric acid levels with significant (P<0.001) decreases in total protein, albumin, potassium, sodium, chloride, and bicarbonate levels were obtained in MTX/CPT-intoxicated rats when compared to control. Furthermore, kidney malondialdehyde levels were significantly (P<0.001) increased whereas catalase, superoxide dismutase, glutathione and glutathione peroxidase levels were significantly (P<0.001) decreased in MTX/CPT-intoxicated rats when compared to control. Pathologic changes marked by atrophic glomeruli were detected in the kidneys of MTX/CPT-treated rats. However, nephrotoxicity observed in MTX/CPT-treated rats was significantly reversed in MT (P<0.01), ALA (P<0.05) and MT+ALA (P<0.001) pretreated rats when compared to MTX/CPT -treated rats. Conclusion: MT and ALA supplementations attenuate nephrotoxicity caused by MTX/CPT.
Highlights
Most anticancer therapies are seldom effective by single anticancer drug due to biologic heterogeneity and multiple genetic alterations stimulating the use of anticancer drug combinations
Implication for health policy/practice/research/medical education: This study discovered that supplementations with melatonin and alpha lipoic acid attenuate kidney injury caused by methotrexate/ cisplatin
This study examined the protective effects of alpha-lipoic acid (ALA) and MT against kidney toxicity induced by MTX/CPT in albino rats
Summary
Most anticancer therapies are seldom effective by single anticancer drug due to biologic heterogeneity and multiple genetic alterations stimulating the use of anticancer drug combinations. Methotrexate/cisplatin (MTX/CPT) has shown beneficial effects in the treatment of metastatic and malignant tumors, but its use may perturb kidney function. Objectives: The present study assessed the protective effects of melatonin (MT) and alpha-lipoic acid (ALA) against kidney toxicity induced by MTX/CPT in albino rats. Anticancer drug cocktail enhances efficacy because it targets key pathways in an additive or synergistic manner This therapeutic approach reduces drug resistance, provides therapeutic anti-cancer benefits such as reducing cancer metastasis, growth and killing rapidly active and dividing cancer cells. Methotrexate and cisplatin (MTX/CPT) combination which has shown comparative advantage over monotherapy is active against cancer with multiple genetic alterations. It has shown efficacy in metastatic penile squamous cell carcinoma [3]. MTX/CPT is an effective regimen for patients with metastatic transitional
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