Empagliﬂozin and neohesperidin protect against methotrexate-induced renal toxicity via suppression of oxidative stress and inflammation in male rats

Osman, Adel T.; Sharkawi, Souty M.Z.; Hassan, Mahdi; Abo-Youssef, Amira M.; Hemeida, Ramadan A.M.

doi:10.1016/j.fct.2021.112406

Cited by 20 publications

(13 citation statements)

References 48 publications

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“…The kidney is also vulnerable to injuries caused by numerous challenges such as ischemia [ 8 , 9 , 10 , 11 , 12 ], drug toxicity [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ], environmental heavy metal exposure [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], hypertension [ 28 , 29 , 30 ], immune injury [ 31 , 32 ], and diabetes [ 33 , 34 , 35 , 36 ]. In terms of environmental risk factors, human kidney disease caused by environmental pollutants and occupational-linked toxins is a major public health issue [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

Cadmium-Induced Kidney Injury: Oxidative Damage as a Unifying Mechanism

Allen

2021

Biomolecules

131

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Cadmium is a nonessential metal that has heavily polluted the environment due to human activities. It can be absorbed into the human body via the gastrointestinal tract, respiratory tract, and the skin, and can cause chronic damage to the kidneys. The main site where cadmium accumulates and causes damage within the nephrons is the proximal tubule. This accumulation can induce dysfunction of the mitochondrial electron transport chain, leading to electron leakage and production of reactive oxygen species (ROS). Cadmium may also impair the function of NADPH oxidase, resulting in another source of ROS. These ROS together can cause oxidative damage to DNA, proteins, and lipids, triggering epithelial cell death and a decline in kidney function. In this article, we also reviewed evidence that the antioxidant power of plant extracts, herbal medicines, and pharmacological agents could ameliorate cadmium-induced kidney injury. Finally, a model of cadmium-induced kidney injury, centering on the notion that oxidative damage is a unifying mechanism of cadmium renal toxicity, is also presented. Given that cadmium exposure is inevitable, further studies using animal models are warranted for a detailed understanding of the mechanism underlying cadmium induced ROS production, and for the identification of more therapeutic targets.

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Section: Introductionmentioning

confidence: 99%

Cadmium-Induced Kidney Injury: Oxidative Damage as a Unifying Mechanism

Allen

2021

Biomolecules

131

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“…Furthermore, the administration of high doses of MTX causes higher drug concentrations in plasma and urine, at an acute and extremely toxic dose the elimination of MTX is delayed execution, then increases the serum creatinine level, and thus is one of the biomarkers of renal failure, this is consistent with the present study. 25,26 Group IV, V, and VI resulted in a significant reduction (P <0.05) in plasma urea and creatinine levels, compared to those levels in group II. That is consistent with the finding of Alshanwani et al, 15 which showed that vitamin B12 improved creatinine clearance levels and renal blood flow, thus, this can reduce creatinine and blood urea nitrogen.…”

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Study of the protective effects of cyanocobalamin on methotrexate induced nephrotoxicity in rats

Abdulwahhab

Alabdali

2022

F1000Res

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Background: Methotrexate (MTX) is a chemotherapeutic drug, used mainly in many cancerous stages, inflammatory and auto-immune diseases, but its use has been limited by its nephrotoxicity. Cyanocobalamin is a water-soluble vitamin possessing nephro-protective properties. The aim of this study was to investigate the effect of cyanocobalamin on the nephrotoxicity of methotrexate. Methods: In this study 42 albino adult female rats were used, divided into six groups each containing seven rats (n=7). First group: Control group (Negative control), 7 rats were injected intraperitoneally with 0.5ml/kg/day NS. Second group: 7 rats were injected intraperitoneal with a single dose of methotrexate (20 mg/kg) for 4 days. Third Group: 7 rats were given intraperitoneal cyanocobalamin at a dose (1.5 mg/kg/day) for two weeks, fourth, fifth, sixth group: 7 rats from each group were injected intraperitoneal with different concentrations of cyanocobalamin (0.5, 1, 1.5 mg/kg /day) respectively for two weeks and MTX (20 mg/kg) which was injected only on day 11. On day 15, rats from all groups were euthanized, and blood samples were taken for biochemical tests, including evaluating serum urea and creatinine. The kidneys were extracted for histological investigation and evaluation of antioxidant (GSH) and oxidative stress (MDA) by using kidney tissue homogenates. Results: This study revealed that kidney damage produced by the MTX (group II) is manifested by significantly elevated (P<0.05) urea and creatinine. On the contrary, the cyanocobalamin groups (IV, V, VI) significantly (P<0.05) reduced urea and creatinine. Renal antioxidant defense systems, such as reduced glutathione depleted by MTX therapy, were restored to normal levels by cyanocobalamin. Furthermore, cyanocobalamin reduced oxidative stress (MDA) and histologically reduced renal tissue injury induced by MTX. Conclusions: In conclusion, the study revealed that cyanocobalamin has a nephroprotective action upon MTX-induced renal damage in rats; cyanocobalamin may offer a protective effect, such as antioxidant action.

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“…Furthermore, the administration of high doses of MTX causes higher drug concentrations in plasma and urine, at an acute and extremely toxic dose the elimination of MTX is delayed execution, then increases the serum creatinine level, and thus is one of the biomarkers of renal failure, this is consistent with the present study. 25,26 Group IV, V, and VI resulted in a significant (P<0.05) reduction (P <0.05) in plasma urea and creatinine levels, compared to those levels in group II. That is consistent with the finding of Alshanwani et al, 24 which showed that vitamin B12 improved creatinine clearance levels and renal blood flow, thus, this can reduce creatinine and blood urea nitrogen.…”

Section: Discussionmentioning

confidence: 85%

Study of the protective effects of cyanocobalamin on methotrexate induced nephrotoxicity in rats

Abdulwahhab

Alabdali²

2022

F1000Res

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Background: Methotrexate (MTX) is a chemotherapeutic drug, used mainly in many cancerous stages, inflammatory and auto-immune diseases, but its use has been limited by its nephrotoxicity. Cyanocobalamin is a water-soluble vitamin possessing nephro-protective properties. The aim of this study was to investigate the effect of cyanocobalamin on the nephrotoxicity of methotrexate. Methods: In the study 42 albino adult female rats were used, divided into six groups each containing seven rats (n=7). 1st group: Control group (Negative control), 7 rats were injected intraperitoneally with 0.5ml/kg/day NS. Second group: 7 rats were injected intraperitoneally with a single dose of methotrexate (20 mg/kg) for 4 days. Third Group: 7 rats were given intraperitoneally cyanocobalamin at a dose (1.5 mg/kg/day) for two weeks, fourth, fifth, sixth group: 7 rats from each group were injected intraperitoneally with different concentrations of cyanocobalamin (0.5, 1, 1.5 mg/kg /day), respectively, for two weeks and MTX (20 mg/kg), which was injected only on day 11. On day 15, rats from all groups were euthanized, and blood samples were taken for biochemical tests, including evaluating serum urea and creatinine. The kidneys were extracted for histological investigation and evaluation of antioxidant (GSH) and oxidative stress (MDA) by using kidney tissue homogenates. Results: This study revealed that kidney damage, produced by the MTX (group II), is manifested by significantly elevated (P<0.05) urea and creatinine. On the contrary, the cyanocobalamin groups (IV, V, VI) significantly (P<0.05) reduced urea and creatinine. Renal antioxidant defense systems, such as reduced glutathione depleted by MTX therapy, were restored to normal levels by cyanocobalamin. Furthermore, cyanocobalamin reduced oxidative stress (MDA) and histologically reduced renal tissue injury induced by MTX. Conclusions: In conclusion, the study revealed that cyanocobalamin has a nephroprotective action upon MTX-induced renal damage in rats; cyanocobalamin may offer a protective effect, such as antioxidant action.

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Empagliﬂozin and neohesperidin protect against methotrexate-induced renal toxicity via suppression of oxidative stress and inflammation in male rats

Cited by 20 publications

References 48 publications

Cadmium-Induced Kidney Injury: Oxidative Damage as a Unifying Mechanism

Cadmium-Induced Kidney Injury: Oxidative Damage as a Unifying Mechanism

Study of the protective effects of cyanocobalamin on methotrexate induced nephrotoxicity in rats

Study of the protective effects of cyanocobalamin on methotrexate induced nephrotoxicity in rats

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