Radioprotective effects of montelukast, a selective leukotriene CysLT1 receptor antagonist, against nephrotoxicity induced by gamma radiation in mice

Abstract

Purpose In this study, we evaluated the renal protective effects of montelukast (MLK) against ionizing radiation (IR) induced nephrotoxicity in mice. Materials and Methods Radioprotective effects of MLK were assessed by biochemical analysis including measurements of kidney malondialdehyde (MDA), reduced glutathione (GSH), and serum creatinine and urea levels. Besides, for further evaluation of protective effects of MLK on renal system, 99mTc‐dimercaptosuccinic acid (DMSA) has been applied. The total antioxidant capacity of MLK was measured by using 1,1‐diphenyl‐2‐picryl hydrazyl radical reagents and compared with butylated hydroxyl toluene standard antioxidant. Results The biochemical evaluation revealed that better results have been achieved for the groups administered with MLK than the only radiation group. Besides only IR‐treated mice group, those treated with MLK demonstrated a significant decrease in urea and creatinine levels. Statistically, significant differences of MDA and SHG levels (P < .05) were found between the radiation group and MLK plus IR‐treated group. Also, 99mTc‐DMSA kidney uptake value (%ID/g) was observed lower for MLK plus IR‐treated mice group than only radiation‐treated mice group. Conclusions According to our findings, MLK has a potential role to be used as a renal protective agent against gamma radiation in radiotherapy.

Radioprotective Effects of Carvacrol and/or Thymol against Gamma Irradiation-Induced Acute Nephropathy: In Silico and In Vivo Evidence of the Involvement of Insulin-like Growth Factor-1 (IGF-1) and Calcitonin Gene-Related Peptide

“…In our study, both carvacrol, thymol, and their combination alleviated renal oxidative stress induced by γ-irradiation, which is consistent with the results of recent studies reporting the radioprotective effects of thymol and carvacrol through an antioxidant mechanism [29,32,35]. In this context, studies have documented the mitigation of radiation-induced oxidative stress when the antioxidative substances were administrated before γ-irradiation, supporting our findings [59,60].…”

“…Even in those cells which did not die from the acute DNA damage, mis-repaired DSBs might induce cell death or cellular senescence and inflammation in the long term [ 67 , 68 ]. Although there is scarcity of data on active inflammation in RN, the inhibition of the renal expressions of NF-κB and TNF-α was found to be involved in the protective effect of montelukast against RN in a dose-dependent manner [ 60 , 69 ]. In our study, the administration of carvacrol or thymol and their combination substantially alleviated the renal inflammation and apoptosis, which is consistent with the results of recent studies [ 70 , 71 ].…”

Suppression of NLRP3 inflammasome activation by astragaloside IV via promotion of mitophagy to ameliorate radiation-induced renal injury in mice

“…Therefore, it is critical to examine the mechanism of IR-induced renal injury and look for effective preventive measures against it. Studies have shown that radiation, including 60 Co-γ rays ( 22 , 23 ), 8-Gy γ rays ( 24 ), cesium-137 rays ( 25 , 26 ), and X-rays ( 27 ), can cause the impairment of renal function and pathological changes. In our study, compared with the control group, the radiation group exhibited significantly increased oxidative damage of the kidneys (increased malondialdehyde, hydrogen peroxide, and advanced oxidation protein products levels; decreased hydrogen peroxide level and total antioxidant capacity), abnormal renal function indices (increased SCr, BUN, cystatin C, N-Gal, and kidney injury molecule-1 levels), and pathological changes of the kidneys (atrophic and fibrotic glomeruli, extensive degeneration and necrosis of the renal tubular epithelial cells, disappearance of brush edges, and vascular congestion).…”

The renoprotective potential of montelukast: a scoping review

“…MLK has the potential to be used as a renal protective agent against gamma radiation in radiotherapy, per the findings of Hormati et al . 76 . A higher level of MDA was detected in IR-treated rats, which is a result of the oxidative stress induced by IR in the kidney.…”