Toxicogenetic profile of rats treated with aqueous extract from Morinda citrifolia fruits

Abstract

Morinda citrifolia ((Family: Rubiaceae)) is extensively used in traditional medicine due to its antiinflammatory, antimicrobial, antitumoral, and anti-hypertensive activities. However, there is no substantial data about hepatotoxic and toxicogenetic effects. This study evaluated biochemical changes and hepatotoxic, genotoxic, and mutagenic effects of aqueous extract of the fruit of M. citrifolia (AEMC) in liver, bone marrow, and peripheral blood cells. Animals (Rattus novergicus, 5 males and 5 females) were divided into negative control, positive control (Cyclophosphamide 25 mg/kg), and AEMC (2.5, 5, and 10 mg/kg, by gavage). AEMC induced increase of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), especially at 10 mg/kg in female (174.8 ± 50.7, 221.4 ± 24.6, and 174.7 ± 14.3 U/L) and male (156.5 ± 21.6, 183.7 ± 21.5, and 147.3 ± 17.8 U/L) (p<0.05). Histological analysis of livers showed inflammatory cell infiltration, nuclear fragmentation, microvacuolization, cellular swelling, points of inflammatoy necrosis, and discrete microvesicular steatosis. DNA damage in hepatocytes was found in both genders, mainly at 10 mg/kg (Frequency of Damage: 78.1 ± 4.5 and 70.4 ± 7.3%; Index of Damage: 107.6 ± 14.2 and 136.0 ± 26.9 for male and female, respectively). Similar results were observed in bone marrow cells. The AEMC 5 and 10 mg/kg induced micronucleus formation (4.4 ± 0.8 and 7.8 ± 1.1; 7.4 ± 1.1 and 9.6 ± 1.4 for peripheral blood and bone marrow cells, respectively) (p<0.05). These findings suggest clastogenic and/or aneugenic effects and genetic instability activated by AEMC, indicating precaution regarding the consumption of formulations or folk preparations based on this plant.