Garlic attenuates chrysotile‐mediated pulmonary toxicity in rats by altering the phase I and phase II drug metabolizing enzyme system

Abstract

Asbestos and its carcinogenic properties have been extensively documented. Asbestos exposure induces diverse cellular events associated with lung injury. Previously, we have shown that treatment with chrysotile shows significant alteration in phase I and phase II drug metabolizing enzyme system. In this study we have examined some potential mechanisms by which garlic treatment attenuates chrysotile-mediated pulmonary toxicity in rat. Female Wistar rats received an intratracheal instillation of 5 mg chrysotile (0.5 mL saline) as well as intragastric garlic treatment (1% body weight (v/w); 6 days per week). Effect of garlic treatment was evaluated after 1, 15, 30, 90, and 180 days by assaying aryl hydrocarbon hydroxylase (AHH), glutathione (GSH), glutathione S-transferase (GST), and production of thiobarbituric acid reactive substances (TBARS) in rat lung microsome. The results showed that AHH and TBARS formation were significantly reduced at day 90 and day 180 in chrysotile treated garlic cofed rats; GSH recovered 15 days later to the near normal level and GST elevated significantly after treatment of garlic as compared to chrysotile alone treated rat lung microsome. The data obtained shows that inhibition of AHH activity and induction of GST activity could be contributing factor in chrysotile-mediated pulmonary toxicity in garlic cofed rats. However, recovery of GSH and inhibition of TBARS formation by garlic and its constituent(s) showed that garlic may give protection by altering the drug metabolizing enzyme system.

Raw and boiled garlic enhances plasma antioxidant activity and improves plasma lipid metabolism in cholesterol-fed rats

“…It is difficult to discuss the results of the influence of garlic extracts, because the preparations (a), amounts (b) and applications (c) were different in each report: (a) homogenization in water of 100 mg/kg/day (Baluchnejadmojarad and Roghani, 2003); (b) 500 mg/kg (Ameen et al, 2003); 250 mg/ kg (Arivazhagan et al, 2004); 2.0 -4.0% dry powder or curcumin (0.2%)/capsaicin (0.015%)/garlic (2.0% dry powder) added to the diets (Kempaiah and Srinivasan, 2004;PedrazaChaverrí et al, 2000;Yeh et al, 2005); (c) intragastric intubation; administration in saline; injection of 1.2 mL/kg body weight/24 h/6 days subcutaneously and intraperitoneally; dried powders as supplementation to diets (Arivazhagan et al, 2004;El-Demerdash et al, 2005;Maldonado et al, 2003;Shin and Kim, 2004).…”

“…Garlic was studied in different forms of extracts: aqueous, ethanol, dried powders (Shin and Kim, 2004;Tsao et al, 2003;Ameen et al, 2003). It was shown that aqueous garlic extract alleviates ischaemia -reperfusion-induced oxidative hepatic injury in rats (Sener et al, 2005).…”

Antioxidants as Potential Therapeutics for Lung Fibrosis

“…Catalytic antioxidants have been shown to have protective effects against silicainduced injury, including the porphyrin MnTBAP (123) and the nitroxide TEMPO (205). Thiol-based antioxidants also have protective effects in the silica-induced injuries, including NAC and GSH (12), as well as garlic extracts that are rich in thiol-containing compounds (6). The lazaroid compounds U-75412E and U-74389G are also effective against silica-induced injury (7,85).…”

Influence of Garlic (Allium sativum) on the Pharmacokinetics of Docetaxel

“…Garlic has been shown to potentially modulate the activity of transferases and cytochrome P450 isozymes, both in vitro and in vivo (8). If these effects occur in patients treated for malignancy, then garlic has the potential to impair the metabolism of many clinically important agents, including the CYP3A4 substrate drug docetaxel ( Fig.…”