Meloxicam induced toxicopathology studies in Wistar rats

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used class of drugs for treating inflammation and pain. Meloxicam has analgesic, anti-inflammatory and antipyretic properties and is a commonly used NSAID in veterinary practice. The present study was done to evaluate effect of meloxicam on toxico-pathological and hematological parameters in Wistar rats. Eighteen Wistar rats were equally divided into three groups i.e. Group I, Group II and Group III. Group I (negative control) rats received only Normal saline (0.9%) @ 1ml/kg. Group II (Low dose) received meloxicam@ 4 mg/kg B.W. and Group III (High dose) rats received meloxicam@8 mg/kg B.W. orally by gavage for 28 days. Dose-dependent clinical signs and lesions were observed after meloxicam treatment. Kidneys and liver were severely hemorrhagic at the high dose, while intestine and stomach had ulcers and erosions. Hematological values were altered after 28 days of administration. Total Erythrocyte Count (TEC), Packed Cell Volume (PCV), Haemoglobin values were decreased and TLC count was significantly increased in both doses of meloxicam treated groups in a dose-dependent manner. It was concluded that meloxicam caused GIT lesions, nephrotoxicity, hepatotoxicity and variation in the hematological parameters at selected dose and duration.

Pharmacokinetics, Milk Residues, and Toxicological Evaluation of a Single High Dose of Meloxicam Administered at 30 mg/kg per os to Lactating Dairy Cattle

“…These organs also showed histopathologic changes, including vacuolar degeneration of hepatocytes with hemorrhage, hyperplasia of intestinal villi projecting into the lumen, sloughing of the glandular epithelium of the stomach and gastric erosions, as well as tubular degeneration and hemorrhage in the kidneys. Blood parameters were also evaluated in the rat study, with the most relevant changes related to the hemorrhage appreciated on a gross exam (decreases in packed cell volume, total erythrocyte count, and hemoglobin) [10]. A single oral dose of 20 mg/kg meloxicam did not result in any toxicologic effects in one study in mice [11], while a separate study in mice receiving 20 mg/kg meloxicam administered subcutaneously resulted in concentration-dependent lesions at the injection site with no evidence of gastric ulceration or kidney or liver lesions [9].…”

“…Blood parameters were evaluated in the llama study, and the most significant change was an increase in mean BUN; however, pre-and post-treatment values were still within the utilized reference range and deemed not clinically relevant [31]. CBC changes were reported in Wistar rats given 8 mg/kg meloxicam per os for 28 days, and the abnormalities were directly related to the post-mortem findings of hemorrhage in multiple tissues [10]. The neutrophil count in the present study was the only parameter with a statistical difference from baseline to the end of the study and with values outside of expected reference ranges.…”

“…There is a growing body of work suggesting that higher and more frequent dosing of NSAIDs may be needed to achieve adequate analgesia in laboratory rodents [7][8][9]. An oral dose of 8 mg/kg was delivered to Wistar rats for 28 continuous days, which resulted in severe ulcerative lesions and hemorrhage in the gastrointestinal tract [10]. However, a single oral dose of 20 mg/kg meloxicam in mice was well tolerated [11].…”