High fructose-containing drinking water-induced steatohepatitis in rats is prevented by the nicotinamide-mediated modulation of redox homeostasis and NADPH-producing enzymes.

An imbalance in the redox state, increased levels of lipid precursors and overactivation of de novo lipogenesis determine the development of fibrosis during nonalcoholic steatohepatitis (NASH). We evaluated the modulation of NADPH-producing enzymes associated with the antifibrotic, antioxidant and antilipemic effects of nicotinamide (NAM) in a model of NASH induced by excess fructose consumption. Male rats were provided drinking water containing 40% fructose for 16 weeks. During the last 12 weeks of fructose administration, water containing NAM was provided to some of the rats for 5 h/day. The biochemical profiles and the ghrelin, leptin, lipoperoxidation and TNF-α levels in serum and the glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME) and NADP+-dependent isocitric dehydrogenase (IDP) levels, the reduced/oxidized glutathione (GSH/GSSG) and reduced/oxidized nicotinamide adenine dinucleotide (phosphate) (NAD(P)H/NAD(P)+) ratios, and the levels of various lipogenic and fibrotic markers in the liver were evaluated. The results showed that hepatic fibrosis induced by fructose consumption was associated with weight gain, hunger-satiety system dysregulation, hyperinsulinemia, dyslipidemia, lipoperoxidation and inflammation. Moreover, increased levels of hepatic G6PD and ME activity and expression, the NAD(P)H/NAD(P)+ ratios, and GSSG concentration and increased expression of lipogenic and fibrotic markers were detected, and these alterations were attenuated by NAM administration. Specifically, NAM diminished the activity and expression of G6PD and ME, and this effect was associated with a decrease in the NADPH/NADP+ ratios, increased GSH levels and decreased lipoperoxidation and inflammation, ameliorating fibrosis and NASH development. NAM reduces liver steatosis and fibrosis by regulating redox homeostasis through a G6PD- and ME-dependent mechanism.

Comparison of the efficacy and safety of a novel meloxicam ophthalmic formulation with a reference diclofenac solution in cataract surgery.

A novel topical ophthalmic formulation of the preferential COX-2 inhibitor meloxicam has recently been developed. The purpose of the present study was to evaluate the efficacy and safety of this novel 0.03% meloxicam solution with regard to a reference 0.1% diclofenac formulation in a prospective, parallel, randomized, multicenter, double-blind study. Two groups of patients submitted to phacoemulsification with intraocular lens implantation were formed. Patients in one group were treated with meloxicam and those in the other group with diclofenac. Dosing was 1 drop t.i.d. for 30 days, beginning the first day after surgery, for both treatments. Inflammation was assessed by the presence of cells in the anterior chamber, anterior chamber flare, ciliary flush, photophobia and pain. Both treatments significantly reduced these indicators. Topical meloxicam and diclofenac produced a similar degree of burning sensation and conjunctival hyperemia. There was no significant difference between treatments in any of the measured parameters. It is concluded that the novel meloxicam solution is effective and safe. Meloxicam, however, did not offer any significant benefit over the diclofenac formulation in patients submitted to cataract surgery.