Role of Phosphodiesterase Enzyme Modulation in Protection of Hepatotoxicity Induced by D-Galactosamine in Rats

Document Type : Original Article

Authors

1 Department of Physiology; Faculty of Pharmacy, Minia University

2 Department of Pharmacology & Toxicology Faculty of Pharmacy, Minia University

Abstract

The study was conducted to investigate possible mechanisms of the hepatoprotective
actions of Pentoxifylline (a non-selective phosphodiesterase inhibitor) against
experimentally induced hepatic injury in rats. The rats were randomly assigned to
vehicle (saline), pentoxifylline (PTX, 100 mg/Kg) and silymarin (SYM, 100mg/Kg)
and combination of the two in the same doses pretreated groups for three weeks, in
addition to the control group. Hepatic injury was induced by intraperitoneal single
dose injection of D-galactosamine (D-GAL, 800mg\kg). Hepatic functions parameters
(serum levels of albumin, and alkaline phosphatase (ALP) activity were determined.
Antioxidants properties of pentoxyphylline were examined via measuring the
antioxidant enzymes activities such as superoxide dismutase (SOD), catalase (CAT),
lipid peroxides as well as hepatic total nitrites. Histopathological findings were, also,
determined using portions of liver tissues. Results showed that the liver injury
induced by D-galactosamine treated rats was improved in the three pretreated groups
to variable extents. Pretreatment with PTX prevented D-galactosamine induced
reduction of antioxidative enzymes, SOD and CAT, and attenuated the elevated MDA
level in hepatic tissue which was observed in non pretreated D-Gal group. These
findings could be attributed to antioxidant activity of PTX and its metabolites effects.
It 'also' caused increase in hepatic triglycerides, normalization of nitric oxide level,
and lowering serum ALP activity and inhibited reduction of serum albumin level
caused by D-Gal, these effects reflect possible hepatoprotective effects of PTX.

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