Nonsteroidal antiinflammatory drugs like ibuprofen impede tissue repair by virtue of retarding inflammation. The present study was undertaken to explore if linking of nitrooxyethyl ester to ibuprofen reverses its healing-depressant propensity. Nitrooxyethyl ester of ibuprofen (NOE-Ibu) was synthesized in our laboratory through a well-established synthetic pathway. NOE-Ibu was screened for its influence on collagenation, wound contraction and epithelialization phases of healing, and scar size of healed wound in three wound models, namely, incision, dead space, and excision wounds. Besides, its influence on the oxidative stress (levels of GSH and TBARS) was also determined in 10-day-old granulation tissue. NOE-Ibu was further screened for its antiinflammatory activity in rat paw edema model. NOE-Ibu promoted collagenation (increase in breaking strength, granulation weight, and collagen content), wound contraction and epithelialization phases of healing. NOE-Ibu also showed a significant antioxidant effect in 10-day-old granulation tissue as compared to ibuprofen. Results vindicate that the esterification of ibuprofen with nitrooxyethyl group reverses the healing-suppressant effect of ibuprofen. The compound also showed equipotent antiinflammatory activity as ibuprofen.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin associated with drug abuse and causes permanent symptoms of Parkinson's disease (PD) by destroying dopaminergic neurons in the substantia nigra of the brain. In the present study, the neuroprotective effects of two carboxylic acid compounds, viz. alpha-ketoglutarate (A-KG), a Kreb's cycle intermediate and ethyl pyruvate (EP), a lipid-soluble analogue of pyruvate, were evaluated against MPTP intoxication in mice and compared with madopar (MD; combination of levodopa plus benserazide), a standard drug. Animals received oral treatment of A-KG (500 mg/kg), EP (100 mg/kg) or MD (5 mg/kg) daily for 5 days followed by intraperitoneal administration of MPTP (20 mg/kg) and posttreatment (+10 min) of A-KG, EP or MD daily for the remaining 5 days. MPTP caused the inhibition of complex I of electron transport chain accompanied by oxidative stress in the brain. It also caused cytotoxicity in the midbrain region as characterized by histology and immunohistochemistry. Treatments of A-KG and EP were found to resolve the loss of motor coordination, oxidative stress, diminished complex I activity and tyrosine hydroxylase-positive neurons in midbrain. A-KG and EP also regressed the histological damage in the brain and minimized the accumulation of alpha-synuclein in the midbrain region. The data suggest that A-KG and EP which are nontoxic carboxylic acid compounds could be of potential therapeutic value in the treatment of PD.

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