Paracetamol (which is a recommended international nonproprietary name of acetaminophen (acetyl-p-aminophenol, APAP)), was synthesized in 1878 by Morse and first introduced into medicine as an antipyretic/analgesic by Von Mering in 1893. 1-3 Initially, it was rarely used in favor of phenacetin. However, after discovering that paracetamol is the main metabolite of phenacetin with better tolerance vs. phenacetin nephrotoxicity, in the 1950s paracetamol replaced phenacetin in use 4-6 and has become a widespread drug since then. Prostaglandins are mainly mediators of inflammatory pain. 7,8 The enzymes responsible for the synthesis of these mediators are called cyclooxygenases. 9 In 1971, John Vane identified the first cyclooxygenase (COX-1). 10 This discovery helped explain the mechanism of action of aspirin, which has been extensively used since 1899 as an analgesic and anti-inflammatory drug. 10 Afterwards, in 1991, Xie et al at Daniel Simmons's laboratory, Brigham Young University, discovered the second cyclooxygenase (COX-2). 11,12 Interestingly, the structure of the COX-2 enzyme did not differ substantially from the previously discovered COX-1. 13 However, they have different clinical significance. 14,15 Finally, in 2002, Chandrasekharan et al discovered

Garlic (Allium sativum L.) has a reputation as a therapeutic agent for many different diseases such as microbial infections, hypertension, hypercholesterolaemia, diabetes, atherosclerosis and cancer. Health benefi ts of garlic depend on its content of biologically-active compounds, which differs between cultivars and geographical regions. The aim of this study was to evaluate and compare the biological activity of aqueous extracts from nine garlic varieties from different countries

No abstract

No abstract

Dibutyl phthalate (di-n-butyl phthalate, DBP) is one of the most commonly used phthalate esters. DBP is widely used as a plasticizer in a variety of household industries and consumer products. Because phthalates are not chemically bound to products, they can easily leak out to enter the environment. DBP can pass through the placental and blood–brain barriers due to its chemical structure, but little is known about its mechanism of action in neuronal cells. This study demonstrated the toxic and apoptotic effects of DBP in mouse neocortical neurons in primary cultures. DBP stimulated caspase-3 and LDH activities as well as ROS formation in a concentration (10 nM–100 µM) and time-dependent (3–48 h) manner. DBP induced ROS formation at nanomolar concentrations, while it activated caspase-3 and LDH activities at micromolar concentrations. The biochemical effects of DBP were accompanied by decreased cell viability and induction of apoptotic bodies. Exposure to DBP reduced Erα and Pparγ mRNA expression levels, which were inversely correlated with protein expression of the receptors. Treatment with DBP enhanced Ahr mRNA expression, which was reflected by the increased AhR protein level observed at 3 h after exposure. ERα, ERβ, and PPARγ antagonists stimulated DBP-induced caspase-3 and LDH activities. AhR silencing demonstrated that DBP-induced apoptosis and neurotoxicity are mediated by AhR, which is consistent with the results from DBP-induced enhancement of AhR mRNA and protein expression. Our study showed that AhR is involved in DBP-induced apoptosis and neurotoxicity, while the ERs and PPARγ signaling pathways are impaired by the phthalate.