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| 1 | Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function显示文摘Background and aim:Cholestasis-associated renal injury or cholemic nephropathy(CN)is a serious clinical problem.Previous studies mentioned that oxidative stress and mitochondrial impairment play a role in CN.There is no specific pharmacological intervention for CN.Metformin is an anti-diabetic drug administered for decades.On the other hand,novel pharmacological properties have emerged for this drug.The effect of metformin on oxidative stress parameters has been well-recognized in different experimental models.It has also been found that metformin positively affected mitochondrial function.The current study aimed to evaluate the effects of metformin in an animal model of CN.Methods:Rats underwent bile duct ligation(BDL)and were treated with metformin(250 and 500 mg/kg)for 14 consecutive days.Two weeks after the BDL operations,urine,serum,and kidney samples were collected and analyzed.Results:Markers of oxidative stress,including reactive oxygen species(ROS)formation,lipid peroxida-tion,protein carbonylation,depleted antioxidant capacity,and decreased glutathione(GSH)levels were detected in BDL animals.Moreover,mitochondrial indices,including adenosine triphosphate(ATP)level,dehydrogenase activity,mitochondrial membrane potential,and mitochondrial permeability,were impaired in the kidney of cholestatic rats.Renal histopathological alterations in cholestatic animals included tubular degeneration and interstitial inflammation,cast formation,and fibrosis.It was found that metformin significantly alleviated oxidative stress and improved mitochondrial indices in the kidney of cholestatic rats.Tissue histopathological alterations were also mitigated in metformin-treated groups.Conclusions:Metformin could be a candidate for managing CN.The nephroprotective role of metformin is primarily associated with its effects on oxidative stress parameters and mitochondrial function. | Mohammad Mehdi Ommati Hamidreza Mohammadi Khadijeh Mousavi Negar Azarpira Omid Farshad Reyhaneh Dehghani Asma Najibi Sedigheh Kamran Hossein Niknahad Reza Heidari | 2021 | Liver Research2021，5，3： | 3 |
| 2 | Factors associated with recurrence of clubfoot treated by the Ponseti method显示文摘AIM To assess several associated factors on the recurrence of clubfoot after successful correction by the Ponseti method. METHODS A total of 115 children with 196 clubfeet deformities, treated by the Ponseti method, were evaluated. Demographic data, family history of clubfoot in firstdegree relatives, maternal educational level and brace compliance were enquired. Based on their medical files, the characteristics of the patients at the time of presentation such as age, possible associated neuromuscular disease or especial syndrome, severity of the deformity according to the Dimeglio grade and Pirani score, residual deformity after previous Ponseti method and number of casts needed for the correction were recorded.RESULTS There were 83 boys(72.2%) and 32 girls(27.8%) with a male to female ratio of 2.6. The mean age at the initiation of treatment was 5.4 d(range: 1 to 60 d). The average number of casts applied to achieve complete correction of all clubfoot deformities was 4.2. Follow-up range was 11 to 60 mo. In total, 39 feet had recurrence with a minimum Dimeglio grade of 1 or Pirani score of 0.5 at the follow-up visit. More recurrence was observed in non-idiopathic clubfoot deformities(P = 0.001), noncompliance to wear braces(P < 0.001), low educational level of mother(P = 0.033), increased number of casts(P < 0.001), and more follow-up periods(P < 0.001). No increase in the possibility of recurrence was observed when the previous unsuccessful casting was further treated using the Ponseti method(P = 0.091). Also, no significant correlation was found for variables of age(P = 0.763), Dimeglio grade(P = 0.875), and Pirani score(P = 0.624) obtaining at the beginning of the serial casting. CONCLUSION Using the Ponseti method, non-idiopathic clubfoot, noncompliance to wear braces, low educational level of mother, increased number of casts and more followup periods had more association to possible increase in recurrence rate after correction of clubfoot deformity. | Mohammad Reza Azarpira Mohammad Jafar Emami Amir Reza Vosoughi Keivan Rahbari | 2016 | World Journal of Clinical Cases2016，4，10： | 2 |
| 3 | Mitigation of cholestasis-associated hepatic and renal injury by edaravone treatment: Evaluation of its effects on oxidative stress and mitochondrial function显示文摘Background and aim:The liver is the primary organ affected by cholestasis,and complications such as renal injury,renal failure,and the need for renal transplantation are associated with cholestatic liver disease.There is substantial evidence indicating that reactive oxygen species(ROS)and mitochondrial impairment are fundamental mechanisms underlying cholestasis-induced hepatic and renal injury.Edaravone(EDV)is a potent radical scavenger and antioxidant that may prevent oxidative stress and improve impaired mitochondrial function in various diseases.This study was performed to evaluate the effects and mechanisms of action of EDV on hepatic and renal injury in an animal model of cholestasis.Methods:Rats subjected to bile duct ligation(BDL)were treated with EDV 1 or 10 mg/kg/day intraper-itoneally for 14 consecutive days.Biomarkers of oxidative stress and mitochondrial impairment in the liver and kidney were assessed in EDV-treated and untreated rats with cholestasis.Results:Significant increases in tissue ROS level,lipid peroxidation,protein carbonylation,and oxidized glutathione level were detected in rats subjected to BDL.Additionally,significant decreases in tissue glutathione level and antioxidant capacity were observed in the hepatic and renal tissues of rats with cholestasis.Markers of mitochondrial impairment,including mitochondrial depolarization,lipid perox-idation,mitochondrial permeabilization,depleted adenosine triphosphate content,and decreased de-hydrogenase activity,were also detected in rats subjected to BDL.Furthermore,portal inflammation,necrosis,and tissue fibrosis were detected in the liver and significant tubular atrophy and interstitial inflammation,as well as fibrotic lesions,were detected in the kidneys of rats with cholestasis.EDV treatment significantly mitigated cholestasis-associated hepatic and renal injury.Conclusions:The antioxidative properties of EDV and its positive effects on the indices of mitochondrial function may be critical factors contributing to protection against cholestasis-associated hepatic and renal injury. | Mohammad Mehdi Ommati Hanie Attari Asma Siavashpour Marzieh Shafaghat Negar Azarpira Hasti Ghaffari Leila Moezi Reza Heidari | 2021 | Liver Research2021，5，3： | 2 |
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