scholarly journals Melatonin and alpha lipoic acid attenuate methotrexate/ cisplatin-induced kidney toxicity in albino rats

2019 ◽  
Vol 9 (2) ◽  
pp. e17-e17
Author(s):  
Elias Adikwu ◽  
Nelson Clement Ebinyo ◽  
Bonsome Bokolo

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.

2019 ◽  
Vol 9 (1) ◽  
pp. e06-e06 ◽  
Author(s):  
Elias Adikwu ◽  
Nelson Brambaifa ◽  
Wolfe Atuboyedia Obianime

Introduction: Lopinavir/ritonavir (LPV/r) may cause renal dysfunction such as electrolyte and acid base disorders and alteration in kidney morphology. Drug–induced renal dysfunction can occur through multiple mechanisms including oxidative stress and inflammation. Objectives: The current study aimed at evaluating the protective effects of melatonin (MT) and alpha lipoic acid (ALA) against serum electrolytes and kidney histology of LPV/r-treated rats. Adult albino rats were randomized into six groups (A to F). Rats in the control groups were treated orally with normal saline and 1% ethanol as placebo and solvent control for 90 days respectively. Rats in the experimental groups were pre-treated orally with 10 mg/kg of MT, 10 mg/kg of ALA, and MT+ ALA daily before treatment with 22.9/5.71, 45.6/11.4 94 and 91.4/22.9 mg/kg/d of LPV/r for 90 days respectively. Materials and Methods: At the end of treatment, rats were euthanized. Blood samples were collected and serum samples were extracted and evaluated for electrolytes, total protein, and albumin. Additionally, kidneys were excised via dissection and evaluated for morphological changes. Results: Significant (P<0.001) decreases in serum sodium, potassium, chloride, bicarbonate, total protein and albumin in a dose-dependent fashion were obtained in LPV/r-treated rats when compared to control. Dose-dependent kidney morphological changes characterised by tubular necroses were obtained in LPV/r-treated rats. The observations in LPV/r-treated rats were significantly reversed in MT (P<0.01), ALA (P<0.01) and MT+ALA (P<0.001) pre-treated rats when compared to LPV/r-treated rats. Conclusion: MT and ALA can serve as adjuvant therapies for LPV/r-associated alterations in serum electrolytes and kidney histology.


Dose-Response ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 155932582110012
Author(s):  
Shaimaa M. Badr-Eldin ◽  
Usama A. Fahmy ◽  
Hibah M. Aldawsari ◽  
Osama A. A. Ahmed ◽  
Nabil A. Alhakamy ◽  
...  

Peptic ulcer disease is an injury of the alimentary tract that leads to a mucosal defect reaching the submucosa. Alpha-lipoic acid (ALA), a natural potent antioxidant, has been known as a gastroprotective drug yet its low bioavailability may restrict its therapeutic efficacy. This study aimed to formulate and optimize ALA using a self-nanoemulsifying drug delivery system (SNEDDS) with a size of nano-range, enhancing its absorption and augmenting its gastric ulcer protection efficacy. Three SNEDDS components were selected as the design factors: the concentrations of the pumpkin oil (X1, 10–30%), the surfactant tween 80 (X2, 20–50%), and the co-surfactant polyethylene glycol 200 (X3, 30–60%). The experimental design for the proposed mixture produced 16 formulations with varying ALA-SNEDDS formulation component percentages. The optimized ALA-SNEDDS formula was investigated for gastric ulcer protective effects by evaluating the ulcer index and by the determination of gastric mucosa oxidative stress parameters. Results revealed that optimized ALA-SNEDDS achieved significant improvement in gastric ulcer index in comparison with raw ALA. Histopathological findings confirmed the protective effect of the formulated optimized ALASNEDDS in comparison with raw ALA. These findings suggest that formulation of ALA in SNEDDS form would be more effective in gastric ulcer protection compared to pure ALA.


2016 ◽  
Vol 62 (2) ◽  
pp. 17-24
Author(s):  
Elias Adikwu ◽  
Brambaifa Nelson ◽  
Wolfe Atuboyedia Obianime

The use of lopinavir/ritonavir (LPV/r) could be associated with testicular toxicity as a limiting factor. The present study evaluated the effects of melatonin (MT) and alpha lipoic (ALA) acid on LPV/r–induced testicular toxicity in male albino rats. Eighty five male albino rats used for this study were randomized into 6 groups (A-F). Rats in groups A1 and A2 served as placebo and solvent control and were orally exposed to water and 1% ethanol, respectively. Rats in group B were exposed to oral doses of MT (10 mg kg-1/day), ALA (10 mg kg-1/day) and combined doses of MT and ALA, respectively. Rats in group C were exposed to oral doses of LPV/r (22.9/5.71 - 91.4/22.9 mg kg-1/ day), respectively. Rats in group D-F were exposed to oral doses of MT (10 mg kg-1/day), ALA (10 mg kg-1/day) and combined doses of MT and ALA prior to oral exposure to LPV/r (22.9/5.71 - 91.4/22.9 mg kg-1/day), respectively. At the end of 60 days of exposure to drugs, rats were sacrificed; blood was collected and serum extracted and evaluated for testosterone. Testes were collected and evaluated for sperm parameters. LPV/r-treated rats showed significant (P<0.05) and dose-dependent decreases in sperm count, sperm motility, sperm viability and serum testosterone levels with increases in abnormal sperm cells, debris, and primordial sperm cells when compared to placebo control. However, LPV/r-induced changes in sperm parameters and serum testosterone levels were attenuated in rats pretreated with MT and ALA. The best effects were observed in rats pretreated with combined doses of MT and ALA. Melatonin and alpha lipoic acid have potential to reduce testicular toxicity associated with lopinavir/ritonavir treatment.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Wei Liu ◽  
Lian-jie Shi ◽  
Sheng-guang Li

Αlpha-lipoic acid is a naturally occurring antioxidant in human body and has been widely used as an antioxidant clinically. Accumulating evidences suggested that α-lipoic acid might have immunomodulatory effects on both adaptive and innate immune systems. This review focuses on the evidences and potential targets involved in the immunomodulatory effects of α-lipoic acid. It highlights the fact that α-lipoic acid may have beneficial effects in autoimmune diseases once the immunomodulatory effects can be confirmed by further investigation.


2007 ◽  
Vol 56 (4) ◽  
pp. 303-310 ◽  
Author(s):  
N TASTEKIN ◽  
N AYDOGDU ◽  
D DOKMECI ◽  
U USTA ◽  
M BIRTANE ◽  
...  

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