Pantothenic Acid Derivatives Modulate Oxidative Stress and Hepatic Fibrosis in Bile Duct Ligation-Induced Cholestatic Liver Injury

Semenovich, Dmitry S.; Abramicheva, Polina A.; Zorova, Ljubava D.; Elchaninov, Andrey V.; Kozlova, Maria A.; Areshidze, David A.; Andrianova, Nadezda V.; Kanunnikova, Nina P.; Moiseenok, Andrey G.; Pevzner, Irina B.; Plotnikov, Egor Y.; Zorov, Dmitry B.

doi:10.3390/pathophysiology33020032

Open AccessArticle

Pantothenic Acid Derivatives Modulate Oxidative Stress and Hepatic Fibrosis in Bile Duct Ligation-Induced Cholestatic Liver Injury

by

Dmitry S. Semenovich

^1,2,*

,

Polina A. Abramicheva

¹,

Ljubava D. Zorova

^1,2

,

Andrey V. Elchaninov

³

,

Maria A. Kozlova

³

,

David A. Areshidze

³

,

Nadezda V. Andrianova

¹

,

Nina P. Kanunnikova

^4,5,

Andrey G. Moiseenok

⁵,

Irina B. Pevzner

^1,2

,

Egor Y. Plotnikov

^1,2,*

and

Dmitry B. Zorov

^1,2

¹

A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia

²

V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, 117997 Moscow, Russia

³

Avtsyn Research Institute of Human Morphology, Federal State Budgetary Scientific Institution “Petrovsky National Research Centre of Surgery”, 117418 Moscow, Russia

⁴

Department of Technology, Physiology and Food Hygiene, Yanka Kupala State University of Grodno, 230022 Grodno, Belarus

⁵

Institute of Biochemistry of Biologically Active Compounds, 230030 Grodno, Belarus

^*

Authors to whom correspondence should be addressed.

Pathophysiology 2026, 33(2), 32; https://doi.org/10.3390/pathophysiology33020032

Submission received: 28 February 2026 / Revised: 8 May 2026 / Accepted: 9 May 2026 / Published: 13 May 2026

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Abstract

Background/Objectives: Inflammation and oxidative stress are key factors contributing to the initiation and progression of liver fibrosis in chronic obstructive cholestasis. Pantothenic acid (PA) and some of its derivatives have been reported to exhibit moderate anti-inflammatory, antioxidant, and regenerative effects. This study aimed to evaluate the redox-modulating effects of PA derivatives—panthenol (PL), pantethine (PT), and hopantenic acid (HPA) in a rat model of chronic obstructive cholestasis induced by common bile duct ligation (BDL). Methods: Macroscopic, histological, and ultrastructural alterations in the liver were assessed, along with molecular markers of oxidative stress, inflammation, and parameters of the glutathione (GSH) system. Results: BDL-induced liver injury was associated with enhanced lipid peroxidation, mitochondrial structural alterations, depletion of GSH, increased levels of protein S-glutathionylation (PSSG), and elevated thiobarbituric acid-reactive substances in mitochondria. Treatment with PL and, to a lesser extent, PT was associated with attenuation of hepatocellular ultrastructural damage, reduced bile duct hyperplasia, decreased inflammatory and necrotic changes, and moderate improvement in fibrosis-related parameters. In contrast, HPA (a PA antagonist) did not demonstrate hepatoprotective effects and it was associated with more pronounced liver injury. Conclusions: Chronic BDL is accompanied by suppression of glutathione redox capacity and enhanced oxidative stress. PL and PT, but not HPA, were associated with reduced levels of protein S-glutathionylation and partial restoration of redox balance. The protective effects of PL and PT may contribute to their antifibrotic activity, potentially through direct antioxidant capacity or redox-modulating mechanisms associated with the GSH system.

Keywords: common bile duct ligation; glutathione system; inflammation; liver fibrosis; lipid peroxidation; panthenol; pantethine; hopantenic acid; obstructive cholestasis; oxidative stress; mitochondria

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MDPI and ACS Style

Semenovich, D.S.; Abramicheva, P.A.; Zorova, L.D.; Elchaninov, A.V.; Kozlova, M.A.; Areshidze, D.A.; Andrianova, N.V.; Kanunnikova, N.P.; Moiseenok, A.G.; Pevzner, I.B.; et al. Pantothenic Acid Derivatives Modulate Oxidative Stress and Hepatic Fibrosis in Bile Duct Ligation-Induced Cholestatic Liver Injury. Pathophysiology 2026, 33, 32. https://doi.org/10.3390/pathophysiology33020032

AMA Style

Semenovich DS, Abramicheva PA, Zorova LD, Elchaninov AV, Kozlova MA, Areshidze DA, Andrianova NV, Kanunnikova NP, Moiseenok AG, Pevzner IB, et al. Pantothenic Acid Derivatives Modulate Oxidative Stress and Hepatic Fibrosis in Bile Duct Ligation-Induced Cholestatic Liver Injury. Pathophysiology. 2026; 33(2):32. https://doi.org/10.3390/pathophysiology33020032

Chicago/Turabian Style

Semenovich, Dmitry S., Polina A. Abramicheva, Ljubava D. Zorova, Andrey V. Elchaninov, Maria A. Kozlova, David A. Areshidze, Nadezda V. Andrianova, Nina P. Kanunnikova, Andrey G. Moiseenok, Irina B. Pevzner, and et al. 2026. "Pantothenic Acid Derivatives Modulate Oxidative Stress and Hepatic Fibrosis in Bile Duct Ligation-Induced Cholestatic Liver Injury" Pathophysiology 33, no. 2: 32. https://doi.org/10.3390/pathophysiology33020032

APA Style

Semenovich, D. S., Abramicheva, P. A., Zorova, L. D., Elchaninov, A. V., Kozlova, M. A., Areshidze, D. A., Andrianova, N. V., Kanunnikova, N. P., Moiseenok, A. G., Pevzner, I. B., Plotnikov, E. Y., & Zorov, D. B. (2026). Pantothenic Acid Derivatives Modulate Oxidative Stress and Hepatic Fibrosis in Bile Duct Ligation-Induced Cholestatic Liver Injury. Pathophysiology, 33(2), 32. https://doi.org/10.3390/pathophysiology33020032

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Pantothenic Acid Derivatives Modulate Oxidative Stress and Hepatic Fibrosis in Bile Duct Ligation-Induced Cholestatic Liver Injury

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