Evaluating the effects of clavulanic acid, a competitive inhibitor of beta-lactamase on the STZ-induced neuropathic pain and potential mechanisms of action in the spinal cord of male rats

Kolahdouz, Mahnoush (2018) Evaluating the effects of clavulanic acid, a competitive inhibitor of beta-lactamase on the STZ-induced neuropathic pain and potential mechanisms of action in the spinal cord of male rats. Masters thesis, Sabzevar University of Medical Sciences.

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Abstract

Introduction: Diabetes mellitus is one of the most common human diseases in the 21st century. Diabetic neuropathy is one of the common complications of diabetes mellitus, seen in 50% of patients. This study was designed to investigate the effect of clavulanic acid, a competitive beta-lactamase inhibitor, on the streptozocin (STZ)-induced neuropathic pain and possible involved mechanisms in the spinal cord of male rats. Materials and Methods: In this experimental study, 48 male Wistar rats were used (250 ± 30 gr). Animals were divided into 6 (n=8) groups: healthy (naive) group, control group which treated with a single dose of intraperitoneal injection of STZ (50 mg/kg), pretreatment groups: animals received clavulanic acid at doses of 10, 20 and 40 mg/kg, one week after STZ injection continued for 10 consecutive days, treatment group: diabetic animals treated with 20 mg/kg of clavulanic acid, 21 days after STZ injection, continued for 10 days. In order to investigate mechanical and cold allodynia which was induced following diabetes-induced neurological damage, Von Frey test and acetone test were used, respectively. Thermal hyperalgesia was performed by tail-flick apparatus. Study of pain behaviors started from the day of STZ injection and continued on days 7, 14, 21,28,35,42 after STZ injection. The Expression of the gene of oxidative factors including iNOS and the expression of the genes involved in the apoptosis including bax, bcl2, caspase3, and glutamate transport 1 (GLT1) expressions were measured by Real Time PCR at day 42 in spinal cord tissue. Results: Twenty one days after STZ injection, diabetic animals have a significant sensitivity to Von Frey stimulants, acetone drop and thermal stimulant compared to the healthy group, which determines mechanical, cold allodynia and thermal hyperalgesia respectively. Intraperitoneal administration of clavulanic acid (10, 20 and 40 mg / kg) improved symptoms of allodynia and hyperalgesia induced in diabetic animals following STZ injection, both in pretreatment and treatment groups. The expression of iNOS, bax to bcl2 ratio, was significantly increased in the spinal cord of diabetic animals which decreased after treatment with clavulanic acid. Caspase3 expression in diabetic animals, as well as in animals treated with clavulanic acid, did not change significantly. In contrast, GLT1 gene that had decreased in the spinal cord of diabetic animals, signifiantly increased after clavulanic acid treatment. Conclusion: Clavulanic acid seems to improve neuropathic pain following diabetes induction and also attenuates pain symptoms in animals suffering from diabetic neuropathic pain. The beneficial effects of this drug may be due to the inhibition of nitrosative stress, increased expression of GLT1 gene and inhibition of some apoptotic mediators.

Item Type:	Thesis (Masters)
Uncontrolled Keywords:	Clavulanic acid, apoptosis, GLT1, Bax, BCL2, Caspase3 and iNOS, neuropathic pain
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User:	Saeed Shoja
Date Deposited:	09 Jan 2019 05:41
Last Modified:	09 Jan 2019 05:41
URI:	http://eprints.medsab.ac.ir/id/eprint/890

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