Mechanisms for redox actions of nicotine and glutathione in cell culture, relevant to periodontitis

Abstract

The oxidative effect of nicotine was investigated using androgen biomarkers of redox status and wound healing in fibroblasts; using the antioxidant glutathione for confirmation of responses. Cultures of human gingival (HGF) and periosteal fibroblasts (HPF) were incubated with substrates 14C-testosterone/14C-4-androstenedione in the presence or absence of serial concentrations of nicotine (N100-500), glutathione (G1–5) and their combinations, in medium. At 24 h the medium was solvent extracted for metabolites, separated by TLC and quantified using radioisotope scanning. Nicotine caused significant inhibition in yields of the physiologically active metabolite 5α-dihydrotestosterone (DHT) in HGF and HPF, overcome to varying degrees by the anti-oxidant glutathione (n = 6; p<0.01, one way ANOVA); this is suggestive of moderation of an oxidative mechanism induced by nicotine. Down-regulation of 5α-reductase activity by nicotine resulting in reduced yields of DHT was overcome by glutathione. Overcoming oxidative stress in a redox environment is applicable to treatment outcome.

Electronic Nicotine Delivery Systems (ENDS) and Their Relevance in Oral Health

“…Oxidative stress was induced by both nicotine-containing and nicotine-free e-liquids with an increase in the expression of pro-apoptotic protein leading to the induction of early and late apoptosis. Oxidative stress generation was more pronounced for nicotine-containing liquid treated samples, as nicotine is known to contribute to the generation of intracellular oxidative stress [58], although also observed for samples treated with nicotine-free fluids compared to the untreated samples and so signifying that the e-liquids composition itself plays a role in increased Bax expression and in triggering of apoptosis in HGFs [57].…”

The antioxidant master glutathione and periodontal health

“…Online Cochrane library database revealed one controlled clinical trial when searched for “glutathione and periodontal.” Pertinent articles in English language on the topic and abstracts of relevant papers were scrutinized thoroughly, and finally papers pertaining to the topic were included after excluding the duplicates [Tables 1 - 5 ]. [ 4 5 28 29 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 …”

“…[ 80 ] Further, the stress-inducible protein heme oxygenase-1 expressed in human gingival fibroblasts exposed to nicotine has been reported to be overcome by the addition of the glutathione precursor N-acetyl-L-cysteine. [ 49 88 ] Minor antioxidative effects have been documented after the application of exogenous glutathione and cysteine, however, whether exogenously applied substances elevated the intracellular glutathione concentrations, still need to be investigated. [ 135 ]…”

Cytotoxicity and apoptosis induction by e-cigarette fluids in human gingival fibroblasts

“…This may be due to an impairment in the defense surveillance of macrophages and neutrophils [6]. One of the major effects of nicotine is the generation of intracellular oxidative stress [7][8][9], leading to cell death via apoptosis through numerous molecules including members of the Bax/bcl-2 family [9,10]. There is morphological evidence of increased oxidative stress-induced apoptosis in HGFs with transient activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERK) and concomitant activation of p38 evidenced by caspase-3 activation, and cleavage of poly ADP ribose polymerase (PARP).…”