Open AccessHEPATOPROTECTIVE EFFECTS OF L-CITRULLINE AGAINST DOXORUBICIN-INDUCED LIVER DAMAGE IN RATS: AN ANALYSIS OF SERUM BIOMARKERS
Author(s) -
Kelvin Theandro Gotama,
Vivian Soetikno,
Melva Louisa,
Wawaimuli Arozal
Publication year - 2019
Publication title -
international journal of applied pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.238
H-Index - 15
ISSN - 0975-7058
DOI - 10.22159/ijap.2019.v11s1.19099
Subject(s) - chemistry , pharmacology , lipid peroxidation , oxidative stress , doxorubicin , citrulline , nitric oxide , toxicity , biochemistry , medicine , arginine , chemotherapy , amino acid , organic chemistry
Objective: The antineoplastic agent doxorubicin (DOX) is known for causing liver toxicity. Its metabolism in hepatocytes causes oxidative stress, which,in turn, induces DNA damage, lipid peroxidation, ATP depletion, and apoptosis. L-citrulline (CIT), a commonly found agent in fruits like watermelon,has piqued interest due to its antioxidant properties. In the body, CIT is converted to nitric oxide, which has been shown to mitigate hepatic injuryby scavenging free radicals, improving hepatic sinusoidal microcirculation, and inhibiting neutrophilic infiltration. This study aims to investigate CITability to prevent DOX-induced hepatotoxicity.Methods: A total of 20 Wistar rats were randomized to receive either DOX (10 mg/kg BW) or NaCl 0.9%. DOX-intoxicated group was further randomizedto either received low-dose CIT (300 mg/kg BW), high-dose CIT (600 mg/kg BW), or aquadest. CIT was given orally for 6 days and DOX throughintraperitoneal injection on days 4 and 5. Serum was obtained and hepatotoxicity was assessed with serum levels of aspartate aminotransferase(AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Statistical analysis was done with one-way ANOVA and Tukey’s test.Results: Serum ALT, AST, and GGT were increased significantly compared to that of normal group. CIT administration in both the doses could decreasethe serum levels of ALT and AST significantly compared to that of DOX group. In this study, CIT in both the doses could reduce the serum levels of GGTcompared to that of DOX group though not statistically significant.Conclusions: This study suggests that CIT exerts hepatoprotective effect, as evident by the attenuation of serum biomarkers.