Effects of Tolfenamic Acid on Oxidative Status, Serum Biochemical, and Hemogram Parameters in Rats

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used group of drugs. Tolfenamic acid is an NSAID with analgesic, anti-inflammatory, and anti-pyretic properties. It exerts its effect by inhibiting prostaglandin synthesis. Considering that NSAIDs may affect oxidative status, liver and kidney function, and hemogram parameters, it was hypothesized in this study that the administration of tolfenamic acid at different doses may affect serum oxidative status, liver and kidney function, and hemogram parameters. The aim of the study is to investigate the effects of tolfenamic acid at different doses on serum oxidative status, biochemical, and hemogram parameters.

Materials, Methods & Results: In the study, 24 healthy female Wistar-Albino rats were equally divided into 4 groups. No treatment was administered to the control group, while the other 3 groups were administered 4, 10, and 20 mg/kg tolfenamic acid intramuscularly for 2 days, respectively. Twenty-four h after the last administration, the animals were anesthetized, blood samples were collected and they were then euthanized. The levels of oxidative status parameters (8-hydroxy-2-deoxyguanosine, malondialdehyde, superoxide dismutase, glutathione peroxidase) in the serum samples were measured using an ELISA reader. Serum aspartate aminotransferase, gamma glutamyl transferase, blood urea nitrogen, cholesterol, calcium, phosphorus, and magnesium levels were measured by using an autoanalyzer, and hemogram parameters (white blood cell, red blood cell, platelet, hemoglobin, hematocrit) were measured by using a hemocell counter. 8-hydroxy-2-deoxyguanosine and glutathione peroxidase levels in the group to which 20 mg/kg tolfenamic acid were higher (P < 0.05) than in the other 3 groups. Lower aspartate aminotransferase and high white blood cell levels in the control group were determined (P < 0.05) than the 20 mg/kg group. Statistical fluctuations (P < 0.05) were observed in red blood cell levels.

Discussion: 8-hydroxy-2-deoxyguanosine, a biomarker for oxidative damage in DNA, and glutathione peroxidase, antioxidant enzyme, levels of the highest dose (20 mg/kg) of tolfenamic acid group were higher than control, 4 mg/kg, and 10 mg/kg groups. This may be due to tolfenamic acid causing DNA damage. The high glutathione peroxidase level may be dependent on tolfenamic acid increased formation of hydrogen peroxide. However, no research could be found regarding the effect of tolfenamic acid on oxidative stress in healthy individuals. Considering the results of the present study, it is understood that NSAID tolfenamic acid does not cause oxidative stress at the recommended doses, but it may cause oxidative stress at the DNA level depending on the dose. Increased aspartate aminotransferase, a marker of liver damage, levels in the highest dose (20 mg/kg) of tolfenamic acid group, were determined. It is known that NSAIDs including tolfenamic acid can cause hepatotoxicity. Elevated liver enzymes may be detected in patients using NSAIDs and enzyme levels should be monitored in patients using NSAIDs. Hence, tolfenamic acid administered at the recommended doses may not cause hepatotoxicity. Hemogram values are used for the diagnosis of selected diseases but occasionally for monitoring the side effects of drugs. Reduced white blood cell and red blood cells count in tolfenamic acid at a dose of 20 mg/kg group that may be related to NSAID caused bleeding. Tolfenamic acid at the recommended doses has no effect on hemogram parameters. However, tolfenamic acid may affect hemogram parameters related to dose. In conclusion, it can be asserted that high-dose tolfenamic acid may cause oxidative stress and liver damage and may reduce hemogram parameters.

Keywords: tolfenamic acid, oxidative status, biochemical values, hemogram.