Journal of Islamic International Medical College (Jun 2021)
Dexamethasone and Pentoxifylline Combination Therapy in Aversion of Lipopolysaccharide Induced Hepatotoxicity In BALB/C Mice
Abstract
Objective: To evaluate the combined effect of dexamethasone, and a phosphodiesterase inhibitor, pentoxifylline, in aversion of LPS/endotoxin induced hepatotoxicity in BALB/c mice. Study Design: Experimental Study. Place and Duration of Study: Department of Pharmacology and Therapeutics, Army Medical College, NUST, Rawalpindi over a period of 3 months (March 2015-June 2015) Materials and Methods: Thirty animals were divided into 5 groups, each group having six animals. The animals were injected intraperitoneally with normal saline (Group 1), lipopolysaccharide(LPS) of serotype E.Coli (Group2), low dose steroid-dexamethasone after LPS (3mg/kg of body weight)(Group 3) , pentoxifylline (PTX) (75 mg/kg of body weight) (Group 4) after LPS and in the last group coadministration of dexamethasone and pentoxifylline after LPS(Group 5).The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue. Results: Lipopolysaccharide administration in animals of Group 2 resulted in marked hepatotoxicity as evident by statistically significantly escalated serum aminotransferases and pronounced inflammation on liver tissue cross section examination. Dexamethasone (Group 3). Pentoxifylline (Group4) and combined treatment (Group 5) abated considerably serum ALT levels at 17 hours when compared to LPS group (Group 1) yielding a p value of ≤ 0.01 for each group. Serum AST levels also declined statistically significantly giving a p value of ≤ 0.01 when LPS group (Group 1) is compared to Group 3, 4 and 5 respectively. Histological examination revealed that Dexamethasone (Group 3). Pentoxifylline (Group 4) and combined treatment (Group 5) reduced inflammation and necrosis produced by LPS in Group 2. However combined treatment results were akin to individual drug therapy alteration. Conclusion: Treatment of lipopolysaccharide (LPS/endotoxin) induced hepatotoxicity with dexamethasone, and phosphodiesterase inhibitor, pentoxifylline in LPS/endotoxin showed encouraging results in our study