The protective effect of nitroglycerin on gastrointestinal and renal side effects of lornoxicam in rats

Eur J Pharmacol. 2006 Jul 17;541(3):191-7. doi: 10.1016/j.ejphar.2006.05.022. Epub 2006 May 22.

Abstract

The aim of this study is firstly, to determine the preventive effect of chronic usage of combination of nitroglycerin and lornoxicam on gastrointestinal and renal side effects and secondly, to investigate the oxidative and antioxidative effects of this combination in rats.

Methods: Thirty-seven Wistar male rats were divided into five groups for 15 days; isotonic group (n = 8, sodium chloride 0.09, Group ISO), lornoxicam group (n = 8, lornoxicam 1.3 mg/kg, Group L), nitroglycerin group (n = 6, nitroglycerin 1 mg/kg, Group NTG), lornoxicam-nitroglycerin combination group (n = 8, 1.3 mg/kg lornoxicam + 1 mg/kg nitroglycerin, Group L-NTG), and control group (n = 7, no drug was administered, Group C). Nitric oxide, malondialdehyde, reduced glutathione (GSH), catalase, interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha concentrations were measured before drug injection and on fifteenth day in all blood samples. Gastrointestinal and renal biopsies were performed on fifteenth day.

Results: Two rats died on tenth and twelfth days in Group L. There were significant differences in Group L compared to the other groups for the lesions of stomach and kidney (p = 0.01, p = 0.028 respectively). Gastric ulceration was occurred in a rat in Group L. Malondialdehyde, TNF-alpha, and IL-6 levels decreased in NTG and L-NTG groups, whereas catalase and glutathion levels increased in NTG, L and L-NTG groups compared to control group (p < 0.05).

Conclusion: Lornoxicam may cause gastrointestinal and renal side effects without oxidative stress. Adding nitroglycerin to lornoxicam for chronic treatment may prevent these side effects and enhance antioxidative effect compared to the use of lornoxicam alone in rats.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity*
  • Catalase / blood
  • Drug Therapy, Combination
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / pathology
  • Gastrointestinal Diseases / pathology
  • Gastrointestinal Diseases / prevention & control*
  • Glutathione / blood
  • Interleukin-6 / blood
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney Diseases / blood
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Male
  • Malondialdehyde / blood
  • Nitroglycerin / therapeutic use*
  • Piroxicam / analogs & derivatives*
  • Piroxicam / toxicity
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / metabolism
  • Vasodilator Agents / therapeutic use*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Vasodilator Agents
  • Piroxicam
  • Malondialdehyde
  • Catalase
  • lornoxicam
  • Nitroglycerin
  • Glutathione