Pentoxifylline mitigates cholestasis-related cholemic nephropathy

Mohammad Mehdi Ommati; Sara Hojatnezhad; Narges Abdoli; Ram Kumar Manthari; Zhipeng Jia; Asma Najibi; Amin Reza Akbarizadeh; Issa Sadeghian; Omid Farshad; Negar Azarpira; Hossein Niknahad; Reza Heidari

doi:10.5114/ceh.2021.111014

eISSN: 2449-8238
ISSN: 2392-1099

Clinical and Experimental Hepatology

Current issue Archive Manuscripts accepted About the journal Editorial board Subscription Contact Instructions for authors Ethical standards and procedures

Editorial System

Submit your Manuscript

Editorial Policies

Sarajevo Declaration on Integrity and Visibility of Scholarly Publications

4/2021
vol. 7

Send email

Copy url:

abstract:

Original paper

Pentoxifylline mitigates cholestasis-related cholemic nephropathy

Mohammad Mehdi Ommati

¹

,

Sara Hojatnezhad

^{2, 3}

,

Narges Abdoli

⁴

,

Ram Kumar Manthari

⁵

,

Zhipeng Jia

⁶

,

Asma Najibi

^{2, 3}

,

Amin Reza Akbarizadeh

⁷

,

Issa Sadeghian

²

,

Omid Farshad

²

,

Negar Azarpira

⁸

,

Hossein Niknahad

^{2, 3}

,

Reza Heidari

²

College of Life Sciences, Shanxi Agricultural University, Taigu, Shanxi, China
Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Iran Food and Drug Administration, Ministry of Health, Tehran, Iran
Department of Biotechnology, GITAM Institute of Science, Gandhi Institute of Technology and Management, Visakhapatnam, Andhra Pradesh, India
College of Animal Sciences and Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, China
Department of Quality Control, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Clin Exp HEPATOL 2021; 7, 4 377-389

DOI: https://doi.org/10.5114/ceh.2021.111014

Online publish date: 2021/11/25

View full text Get citation

PlumX metrics:

Introduction
Cholestasis is the stoppage of bile flow that primarily affects liver function. On the other hand, kidneys are also severely influenced during cholestasis. Cholestasis-induced kidney injury is known as cholemic nephropathy (CN). There is no precise pharmacological option in CN. Previous studies revealed that oxidative stress plays a crucial role in the pathogenesis of CN. On the other hand, the positive effects of pentoxifylline (PTX) against renal injury with different etiologies have been frequently reported. In the current study, the potential nephroprotective role of PTX in cholestasis-induced renal injury is investigated.

Material and methods
Bile duct ligated (BDL) rats were treated with PTX (10, 50, and 100 mg/kg), and renal markers of oxidative stress, urine level of inflammatory cytokines, as well as renal histopathological alterations were monitored.

Results
Significant changes in oxidative stress markers were detected in the BDL group. On the other hand, it was found that PTX (10, 50, and 100 mg/kg) significantly ameliorated cholestasis-induced oxidative stress in renal tissue. Renal histopathological changes, including interstitial inflammation, tubular atrophy, fibrosis, and cast formation, were detected in the BDL rats. Moreover, urine pro-inflammatory cytokines [interleukin (IL)-1, IL-9, IL-18, tumor necrosis factor a (TNF-a), and interferon g (INF-g)] were significantly increased in the cholestatic animals. PTX (10, 50, and 100 mg/kg, 14 days) significantly ameliorated renal histopathological alterations and urine levels of inflammatory cytokines.

Conclusions
These data indicate a potential nephroprotective role for PTX in cholestasis. The effects of PTX on oxidative stress parameters and the inflammatory response could play a primary role in its renoprotective mechanisms.

keywords:

Pentoxifylline mitigates cholestasis-related cholemic nephropathy

Mohammad Mehdi Ommati 1 , Sara Hojatnezhad 2, 3 , Narges Abdoli 4 , Ram Kumar Manthari 5 , Zhipeng Jia 6 , Asma Najibi 2, 3 , Amin Reza Akbarizadeh 7 , Issa Sadeghian 2 , Omid Farshad 2 , Negar Azarpira 8 , Hossein Niknahad 2, 3 , Reza Heidari 2

acute kidney injury, cholestasis, cirrhosis, inflammation, oxidative stress