Reversal of neurobehavioral and neurochemical alterations in STZ-induced diabetic rats by FeTMPyP, a peroxynitrite decomposition catalyst and 1,5-Isoquinolinediol a poly(ADP-ribose) polymerase inhibitor

Abstract

Objective:

In this study, we have evaluated the involvement of nitrosative stress and poly-ADP ribosyl polymerase (PARP) in diabetes induced neurobehavioral and neurochemical changes using pharmacological agents peroxynitrite decomposition catalyst (FeTMPyP) and a PARP inhibitor (1,5-Isoquinolinediol) in diabetic brains.

Methods:

The extent of neurobehavioral changes was assessed by functional observation battery, motor coordination activity (rota rod performance) and passive avoidance test. Neurochemical changes were assessed by measuring nicotinamide adenine dinucleotide (NAD), malondialdehyde, acetylcholinesterase, neurotransmitters (GABA and glutamate) levels in the hippocampus. GABA and glutamate were measured by high-performance liquid chromatography with electrochemical detection method.

Results:

Two weeks’ treatment with FeTMPyP (3 mg/kg, i.p.) and 1,5-Isoquinolinediol (3 mg/kg, i.p.) improved the cognitive deficits in diabetic rats as observed in passive avoidance test. Both the agents inhibited lipid peroxidation and improves the acetylcholinesterase level in the hippocampus. 1,5-Isoquinolinediol treatment also improves the NAD, neurotransmitter level in the hippocampus.

Discussion:

These results suggest that peroxynitrite decomposition catalyst and PARP inhibitor have beneficial effects in neurobehavioral alterations induced by diabetes. Improvement in neurobehavioral alteration may be attributed to reversal of neurotransmitter homeostasis deficits.

Keywords:

• FeTMPyP
• 1
• 5-Isoquinolinediol
• Nitrosative stress
• PARP
• Peroxynitrite
• Diabetes

Acknowledgements

The authors would like to thank the Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Government of India for financial support. Mr Ashok Kumar Datusalia is a recipient of UGC research fellowship.