Anti-inflammatory Effects of Diazepam on Different Models of Inflammation: Roles ofPeripheral Benzodiazepine Receptors and Genes for Corticosterone, Nitric Oxide andCytokines Biosynthesis

Background: It was reported that Peripheral Benzodiazepine Receptors (PBRs) agonists as diazepam possesses immunomodulatory and anti-inflammatory activities that suppress inflammation.

Aim of the study: This study aims to investigate the anti-inflammatory effects of diazepam on the different inflammatory responses in the rats with exploring the possible underlying mechanisms.

Methods and animals: 88 Albino rats used in acute and chronic inflammatory study of carrageenan–induced inflammatory paw edema of the rats (CIPE), and Freund’s adjuvant induced polyarthritis in rats respectively. Tested rat groups in both models received diazepam (I.P). Bilateral adrenalectomy was done in some rat groups of acute and chronic models as reference groups to diazepam treated groups with intact adrenals glands, and indomethacin was used as a reference anti-inflammatory agent in acute and chronic models of inflammation. The hind paw thickness and plasma Nitric Oxide (NOx) were assessed in each sub-groups of acute inflammatory response. The chronic inflammatory response was assessed by measuring the paw thickness, serum C-reactive protein, serum albumin and serum corticosterone of these arthritic rats.

Results: Diazepam significantly reduced the increase in the paw thickness as well as NOx levels compared to other groups of acute study. Administration of diazepam for arthritic rats significantly decreased paw thickness, reduced increase in C-reactive protein, increased serum albumin, and increased serum corticosterone in comparison to administration of indomethacin to the arthritic rats. Diazepam had no any inhibitory anti-inflammatory actions on paw edema thickness, and on others measured serum biochemical when administrated to adrenalectomized rats in both acute and chronic inflammatory studies.

Conclusion: Diazepam through enhancement of activity of genes responsible for synthesis of corticosterone via its stimulatory action on Peripheral Benzodiazepine Receptors (PBRs) in adrenal glands and modulating activity of immune cells could be of high pharmacological interest as a potential anti-inflammatory agent.

Author(s):

Ahmed Abdul-Sabour Bader, Adel Hussein Omar and Mahmoud Hamd El-Odemi

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