title: Perillyl alcohol improves functional and histological outcomes against ischemia-reperfusion injury by attenuation of oxidative stress and repression of COX-2, NOS-2 and NF-κB in middle cerebral artery occlusion rats.
abstract: Perillyl alcohol (PA) is a monoterpene found in essential oils of mints, cherries, citreous fruits and lemon grass, reported to have antioxidant and anti-inflammatory properties. However, the role of PA in stroke is still illusive. Since oxidative stress and inflammation play a pivotal role in ischemia-reperfusion (I-R) injury, this study was designed to elucidate the potential effects of PA against I-R induced pathology in rat׳s brain. Middle cerebral artery occlusion (MCAO) for 2h followed by 22h reperfusion in Wistar male rats (250-280g, 14-16 weeks old) induced the behavioral and histological alterations along with exhausted antioxidant status and enhanced inflammatory mediators. However, PA administration (25, 50 and 100mg/kg b.wt orally once daily for 7 days) prior to MCAO significantly attenuated neurological deficits related to flexion test and spontaneous motor activity, improved grip strength and motor coordination in a dose dependent manner. PA treatment also inhibited oxidative stress in MCAO rats as evident from decreased lipid peroxidation and augmented level of reduced glutathione and restored activities of catalase, glutathione peroxidase, and glutathione reductase and thus, reduced infarct volume and protected the brain histology after I-R injury. Furthermore, PA markedly suppressed the level of proinflammatory cytokines (IL-1β, TNF α and IL-6) and down regulated expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (NOS-2) and nuclear factor κB (NF-κB) in MCAO group. In conclusion, PA mediates neuroprotection against I-R injury via mitigation of oxidative stress and inflammation and thus, may be a good therapeutic approach in stroke prone patient.
authors.affiliation: Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology (DST-FIST and UGC-SAP-BSR funded department), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Rizwana
authors.initials: R
authors.lastname: Tabassum
authors.affiliation: Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology (DST-FIST and UGC-SAP-BSR funded department), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Kumar
authors.initials: K
authors.lastname: Vaibhav
authors.affiliation: Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology (DST-FIST and UGC-SAP-BSR funded department), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Shrivastava
authors.affiliation: Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology (DST-FIST and UGC-SAP-BSR funded department), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Andleeb
authors.initials: A
authors.lastname: Khan
authors.affiliation: Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology (DST-FIST and UGC-SAP-BSR funded department), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Mohd Ejaz
authors.initials: ME
authors.lastname: Ahmed
authors.affiliation: Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology (DST-FIST and UGC-SAP-BSR funded department), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ashafaq
authors.affiliation: Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology (DST-FIST and UGC-SAP-BSR funded department), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: M Badruzzaman
authors.initials: MB
authors.lastname: Khan
authors.affiliation: Department of Biotechnology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Farah
authors.initials: F
authors.lastname: Islam
authors.affiliation: Neuroscience and Toxicology Unit, Faculty of Pharmacy, Jazan University, Jazan, Kingdom of Saudi Arabia.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Safhi
authors.affiliation: Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology (DST-FIST and UGC-SAP-BSR funded department), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India. Electronic address: drfislam@gmail.com.
authors.forename: Fakhrul
authors.initials: F
authors.lastname: Islam
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D039821:Monoterpenes / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*
chemical_list: D016207:Cytokines; D039821:Monoterpenes; D016328:NF-kappa B; D018696:Neuroprotective Agents; C032208:perillyl alcohol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: Behavior; Inflammation; Ischemia–reperfusion; Middle cerebral artery occlusion; Oxidative stress; Perillyl alcohol