Abstract
Cholestasis-associated renal injury, known as cholemic nephropathy (CN), is a severe clinical complication. CN could lead to acute kidney injury. However, there is no specific pharmacological intervention for cholestasis-induced renal injury. Oxidative stress and mitochondrial impairment seem to play a role in the pathogenesis of CN. Betaine (3-methyl glycine; BET) is an amino acid derivative with a wide range of pharmacological actions. Several studies mentioned the effects of BET on oxidative stress in different experimental models. It has also been found that BET positively affected mitochondrial function. The current study aimed to evaluate the effects of BET supplementation on CN in the bile duct ligation (BDL) model of cholestasis. BET (0.25% and 1% w: v in drinking water) was administered to BDL animals for seven consecutive days. Biomarkers of oxidative stress and mitochondrial indices were evaluated in cholestatic animals. Significant elevation in reactive oxygen species formation, lipid peroxidation, and oxidized glutathione (GSSG) was evident in BDL rats. Moreover, reduced glutathione (GSH) levels and renal antioxidant capacity were decreased in cholestatic animals. Mitochondrial depolarization, mitochondrial permeabilization, decreased mitochondrial dehydrogenases activity, and lipid peroxidation was also detected in the kidney of BDL rats. Tubular atrophy, interstitial inflammation, and renal fibrosis were also detected in BDL rats. BET alleviated biomarkers of oxidative stress, improved mitochondrial indices, and decreased renal histopathological alterations in BDL animals. The antioxidant effects and the positive effects of BET on cellular mitochondria seem to play a fundamental role in its nephroprotective role during cholestasis.
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Abbreviations
- ΔΨ:
-
Mitochondrial membrane potential
- ATP:
-
Adenosine tri-phosphate
- BDL:
-
Bile duct ligation
- BET:
-
Betaine
- CN:
-
Cholemic nephropathy
- HPLC:
-
High-performance liquid chromatography
- TBARS:
-
Thiobarbituric acid reactive substances
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Acknowledgements
This investigation was financially supported by the Vice-Chancellor of Research Affairs of Shiraz University of Medical Sciences (Grant No.: 98-01-36-19445), Shiraz, Iran, by the last author (Dr. Reza Heidari); and Shanxi Agricultural University (SXAU, Grant No.: 2018YJ33 (National Natural Science Foundation) and K271999031 (Outstanding Doctors Volunteering to Work in Shanxi Province), Shanxi, China, by the first author (Dr. Mohammad Mehdi Ommati). Authors thank the Pharmaceutical Sciences Research Center (PSRC) of Shiraz University of Medical Sciences and Life Sciences Department of SXAU for providing technical facilities to carry out this study.
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Ommati, M.M., Farshad, O., Azarpira, N. et al. Betaine alleviates cholestasis-associated renal injury by mitigating oxidative stress and enhancing mitochondrial function. Biologia 76, 351–365 (2021). https://doi.org/10.2478/s11756-020-00576-x
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DOI: https://doi.org/10.2478/s11756-020-00576-x