PM2.5 Exposure Elicits Oxidative Stress Responses and Mitochondrial Apoptosis Pathway Activation in HaCaT Keratinocytes.

BACKGROUND:: PM2.5 (aerodynamic diameter ≤ 2.5 µm) is a dominant and ubiquitous air pollutant that has become a global concern as PM2.5 exposure has been linked to many adverse health effects including cardiovascular and pulmonary diseases. Emerging evidence supports a correlation between increased air PM2.5 levels and skin disorders although reports on the underlying pathophysiological mechanisms are limited. Oxidative stress is the most common mechanism of PM2.5-induced adverse health effects. This study aimed to investigate PM2.5-induced oxidative damage and apoptosis in immortalized human keratinocyte (HaCaT) cells. METHODS:: HaCaT cells were exposed to 0, 25, 50, 100, or 200 µg/ml PM2.5 for 24 h. Reactive oxygen species (ROS) generation, lipid peroxidation products, antioxidant activity, DNA damage, apoptotic protein expression, and cell apoptosis were measured. RESULTS:: PM2.5 exposure (0-200 µg/ml) for 24 h resulted in increased ROS levels (arbitrary unit: 201.00 ± 19.28, 264.50 ± 17.91, 305.05 ± 19.57, 427.95 ± 18.32, and 436.70 ± 17.77) and malondialdehyde production (0.54 ± 0.05 nmol/mg prot, 0.61 ± 0.06 nmol/mg prot, 0.68 ± 0.05 nmol/mg prot, 0.70 ± 0.05 nmol/mg prot, and 0.76 ± 0.05 nmol/mg prot), diminished superoxide dismutase activity (6.47 ± 0.28 NU/mg prot, 5.97 ± 0.30 NU/mg prot, 5.15 ± 0.42 NU/mg prot, 4.08 ± 0.20 NU/mg prot, and 3.76 ± 0.37 NU/mg prot), and increased DNA damage and apoptosis in a dose-dependent manner in HaCaT cells. Moreover, cytochrome-c, caspase-3, and caspase-9 expression also increased proportionately with PM2.5 dosing. CONCLUSION:: PM2.5 might elicit oxidative stress and mitochondria-dependent apoptosis that likely manifests as skin irritation and damage.

Zinc(II)-curcumin accelerates the healing of acetic acid-induced chronic gastric ulcers in rats by decreasing oxidative stress and downregulation of matrix metalloproteinase-9.

Gastric ulcers form as a result of a multifaceted process which includes acid secretion, reactive oxygen species generation and extracellular matrix (ECM) degradation. The aim of this study was to investigate the possible mechanisms underlying the anti-ulcerogenic effects of the Zn(II)-curcumin complex, a curcumin derivative, on the healing of acetic acid-induced gastric ulcers in rats. The severely ulcerated gastric mucosa of control animals had a lower glutathione level (GSH) and superoxide dismutase activity (SOD), and increased malondialdehyde (MDA) content compared to sham operated rats (P<0.001). Zn(II)-curcumin solid dispersions (equivalent to 12, 24 and 48 mg/kg) dose-dependently reduced the gastric ulcer index, significantly increased SOD activity and GSH levels, and reduced the MDA content and matrix metalloproteinase-9 (MMP-9) mRNA expression in the gastric mucosa (P<0.05, compared to control animals). Zn(II)-curcumin exerted a greater anti-ulcerogenic effect than curcumin at the same dose (24 mg/kg), leading to a reduced severity of gastric ulcers, lower MDA content, and increased SOD activity and GSH levels (P<0.05). In conclusion, these results confirm that the Zn(II)-curcumin complex possesses an enhanced mucosal barrier defense activity compared to curcumin alone, due to its synergistic ability to decrease oxidative stress and attenuate MMP-9-mediated inflammation.