b-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contain a b-lactam ring in their molecular structures. Synthesis of b-lactam analogs, which are containing dichloride atoms and N-methyl, N-aromatic rings, was achieved by Schiff bases and dichloroketene compounds. All the synthesized imines and b-lactam analogs were tested against two physiologically relevant carbonic anhydrase isozymes (hCA I and II) and acetylcholinesterase (AChE). They demponstrated effective inhibitory profiles with K i values in ranging of 3.22-11.18 nM against hCA I, 3.74-10.41 nM against hCA II, and 0.50-1.57 nM against AChE. On the other hand, acetazolamide and dorzolamide clinically used as CA inhibitors, showed K i value of 170.34 and 129.26 nM against hCA I, and 115.43 and 135.67 nM against hCA II, respectively. Also, tacrine used as standard AChE inhibitor showed K i value of 5.70 nM against AChE.
Free radical production related with many stress factors including radiation, drugs, ageing and trauma plays a key role in cell death. Notwithstanding, free radicals can cause pathology in a variety of diseases through oxidative stress Under oxidative stress, excessive production of free radicals can trigger cell death by primarily DNA and all cellular macromolecule damages. Also, excessive free radicals have a role in early inducers of autophagy cell death upon nutrient deprivation. Autophagy is physiologic process of eukaryotic systems, which have signiicant role in adaptation to oxidative stress by degradation of metalloproteins and oxidatively damaged macromolecules. By oxidizing, membrane injuries allow the leakage of enzymes and contribute to cell damage. However, recent publications demonstrate the protecting role of lysosome system during excessive reactive oxygen species ROS production by the elimination of damaged proteins or organelles. Activation of autophagic or lysosomal system can eliminate the oxidizing components of cell in oxidative stress response. This chapter aims to provide the novel insight data for oxidative damage-mediated autophagy as well as their metabolic networks.
Cisplatin (CDDP), one of the most active cytotoxic agents against cancer, has adverse side effects, such as nephrotoxicity and hepatotoxicity. The present study was designed to investigate the potential protective effect of pomegranate seed extract (PSE) against oxidative stress caused by CDDP injury of the kidneys and liver by measuring tissue biochemical and antioxidant variables and immunohistochemically testing caspase-3-positive cells. Twenty-four Sprague-Dawley rats were divided into 4 groups: control; CDDP: injected intraperitoneally with CDDP (7 mg/kg body weight, single dose); PSE: treated for 15 consecutive days by gavage with PSE (300 mg/kg per day); and PSE+CDDP: treated by gavage with PSE 15 days after a single injection of CDDP. The degree of protection against CDDP injury afforded by PSE was evaluated by determining the levels of malondialdehyde as a measure of lipid peroxidation. The levels of glutathione and activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase were estimated from liver and kidney homogenates; the liver and kidney were also histologically examined. PSE elicited a significant protective effect toward liver and kidney by decreasing the level of lipid peroxidation; elevating the levels of glutathione S-transferase; and increasing the activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase. These biochemical observations were supported by immunohistochemical findings and suggested that PSE significantly attenuated nephrotoxicity and hepatotoxicity by the way of its antioxidant, radical-scavenging, and antiapoptotic effects. This PSE extract could be used as a dietary supplement in patients receiving chemotherapy medications.
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