News Update on biochemical mechanisms : Dec 2021

Biochemical mechanisms of drug action: what does it take for success?

Drug discovery is extremely difficult. There are many unanticipated scientific, medical and business challenges to every drug discovery programme. It is important to increase our understanding of the fundamental properties of effective drugs so that we can anticipate potential problems in developing new agents. This article addresses potential drug discovery and development risks associated with the biochemical mechanism of drug action, and proposes simple rules to minimize these risks. [1]

Biochemical Mechanisms of Cisplatin Cytotoxicity

Since the discovery by Rosenberg and collaborators of the antitumor activity of cisplatin 35 years ago, three platinum antitumor drugs (cisplatin, carboplatin and oxaliplatin) have enjoyed a huge clinical and commercial hit. Ever since the initial discovery of the anticancer activity of cisplatin, major efforts have been devoted to elucidate the biochemical mechanisms of antitumor activity of cisplatin in order to be able to rationally design novel platinum based drugs with superior pharmacological profiles. In this report we attempt to provide a current picture of the known facts pertaining to the mechanism of action of the drug, including those involved in drug uptake, DNA damage signals transduction, and cell death through apoptosis or necrosis. A deep knowledge of the biochemical mechanisms, which are triggered in the tumor cell in response to cisplatin injury not only may lead to the design of more efficient platinum antitumor drugs but also may provide new therapeutic strategies based on the biochemical modulation of cisplatin activity. [2]

Biochemical Mechanisms: Metabolism, Adaptation, and Toxicity

This chapter provides the reader with a fundamental understanding of the systems, including specific nuances observed in aquatic organisms, to describe how these systems provide a degree of adaptation to chemicals, and to illustrate how responses associated with the systems may provide useful tools for problem solving in aquatic toxicology. In the realm of “traditional” toxicology, the study of biochemical phenomena occupies a central position. Elucidations of the biotransformation or metabolism of chemical compounds into more or less toxic products, of the underlying modes of toxic action, and of early biochemical responses have been accepted as critical to the informed diagnosis of human exposures to chemicals, as well as to the development of clinical treatments to counteract toxic effects. Studies in the mammalian literature indicate that under conditions of low oxygen tension, cytochrome P450 can catalyze reduction reactions in which substrate rather than molecular oxygen accepts electrons and is reduced. [3]

Strategies and Mechanisms of Building up and Stabilizing Organic Matter Stocks in Soils

Soil organic matter (SOM) has very important functions in the soil. It affects the soil physical, chemical and biological properties, and eventually affecting the overall soil and crop productivity. Increase in SOM matter is associated with an increase in soil and crop productivity. It also contributes to climate change mitigation through soil carbon sequestration. This paper discusses various soil management and/or farming strategies that contribute to the building up of SOM. The paper also highlights mechanisms that stabilize organic matter in the soil and protect it from rapid decomposition and its loss from the soil. Through reviewing of various research papers, literature shows that a number of strategies provide substantial contributions to building up of SOM. These include: conservation agriculture, crop rotations, cover cropping, agroforestry and afforestration, improved fallows, well managed pastures and organic farming. Various physical, chemical and biochemical mechanisms contribute to stabilization of organic matter and protect the accumulated SOM from rapid decomposition. Quantity and quality of organic materials, soil matrix and clay minerals, organo-mineral interactions and soil management practices are all important factors in SOM stabilization. From this review it can be pointed out that research based knowledge of both SOM accumulation strategies and SOM stabilizing mechanisms is very beneficial in making recommendations and implementation of soil management practices that can increase and build up organic matter in the soil. [4]

Neuroprotective Mechanism of Ethanolic Extract of Irvingia gabonensis Stem Bark against Cadmium-induced Neurotoxicity in Rats

Objective: To explore the neuroprotective effect of Irvingia gabonensis (IG) against cadmium-induced oxidative damage in rats brain.

Place and Duration of Study: Department of Chemical sciences, (Biochemistry laboratory), Afe Babalola University and Department of Biochemistry, Ekiti State University, Ado Ekiti, Nigeria between February 2014 and May 2014.

Methods: The study was performed on twenty (20) male rats divided into four groups: a control group, cadmium group (4mgkg-1day-1, intraperitoneally [i.p.]) and cadmium toxication groups received 200 and 400mgkg-1 body weight of extract by oral gavage for 28 days. The degree of protection in brain tissue was evaluated by the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase, and catalase. The aminotransferase (ALT), aspartate aminotransferase (AST) activities and histological examination were monitored.

Results: Irvingia gabonensis showed a significant (P>.05) brain-protective effect by decreasing the level of lipid peroxidation and elevate the activities of antioxidative enzymes and level of GSH. Furthermore, histological alterations in brain were observed in cadmium untreated rats and were ameliorated in cadmium-induced treated rats with IG.

Conclusions: Consequently Irvingia gabonensis blocked oxidative brain damage induced by cadmium in rats. These data suggest that Irvingia gabonensis extract may play a very useful role in reduction of the neurotoxicological damage induced by cadmium. [5]

Reference

[1] Swinney, D.C., 2004. Biochemical mechanisms of drug action: what does it take for success?. Nature reviews Drug discovery, 3(9), pp.801-808.

[2] Cepeda, V., Fuertes, M.A., Castilla, J., Alonso, C., Quevedo, C. and Pérez, J.M., 2007. Biochemical mechanisms of cisplatin cytotoxicity. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 7(1), pp.3-18.

[3] Di Giulio, R.T., Benson, W.H., Sanders, B.M. and Van Veld, P.A., 2020. Biochemical mechanisms: metabolism, adaptation, and toxicity. In Fundamentals of aquatic toxicology (pp. 523-561). CRC Press.

[4] Njira, K.O.W. and Nabwami, J., 2013. Strategies and Mechanisms of Building up and Stabilizing Organic Matter Stocks in Soils. International Journal of Plant & Soil Science, pp.133-143.

[5] Ojo, O.A., Oyinloye, B.E., Ajiboye, B.O. and Onikanni, S.A., 2014. Neuroprotective mechanism of ethanolic extract of Irvingia gabonensis stem bark against cadmium-induced neurotoxicity in rats. Journal of Advances in Medicine and Medical Research, pp.5793-5805.