Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.

Abstract

Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCI and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans. -Environ Health Perspect 102(Suppl 10): 137-148 (1994)

Effect of dl-α-lipoic acid on cyclophosphamide induced lysosomal changes in oxidative cardiotoxicity

“…These properties of LA may correct the energy demand deficit in myocytes. Giri et al (1994) have reported that Taurine and Niacin could ameliorate the pathogenesis of bleomycin-induced lung fibrosis with an increase in lung collagen reactivity. They have attributed the replenishment of NAD and ATP to repair the ROS mediated injured pulmonary epithelium as one of the possible mechanisms of protection afforded by niacin.…”

Why Is Taurine Cytoprotective?

“…Unfortunately, most studies that have examined the effect of taurine on the anti-oxidant defenses were initially designed to evaluate its effectiveness in reversing the actions of a toxic xenobiotic. In one such study, Giri et al 40 found that bleomycin increased the activity of superoxide dismutase in hamster lung but the increase was prevented in hamsters fed a diet containing elevated levels of taurine and niacin. Nonetheless, there are a handful of studies that have directly tested the effects of taurine on the anti-oxidant defenses.…”

“…production 48 • Another important property of N-chlorotaurine is the ability to regulate the severity of the inflammatory response 40 .4 9 ' 50 . Several groups have shown that Nchlorotaurine downregulates the generation of inflammatory mediators, such as superoxide, nitric oxide, tumor necrosis factor-a, interleukin-6 and prostaglandin E2 51 -53 • It also inhibits the expression of chemokines involved in the recruitment of neutrophils into the lung during pulmonary inflammation 54 • Moreover, there is some evidence that taurine may reduce neutrophil activation and adherence to endothelial cells.…”

Interaction of long-chain nicotinates with dipalmitoylphosphatidylcholine

“…Besides being the precursor of cofactors to many vital enzymes, nicotinic acid is a drug possessing vasodilating and fibrinolytic properties. Nicotinic acid itself has been proven beneficial against bleomycin-and cyclophosphamide-induced lung injury in animal models (1)(2)(3)(4)(5). Dietary supplements of nicotinic acid and dermatologic formulations of its longchain esters are under investigation for the prevention and treatment of skin carcinogenesis (6).…”