EFFECT OF Plectranthus wightii METHANOL EXTRACT AGAINST GENTAMICIN-INDUCED NEPHROTOXICITY IN RATS
V. R. Mohan, A. Doss, P. S. Tresina in Ethnomedicinal Plants with Therapeutic Properties, 2019
The liver is the most important organ in the body. It plays a pivotal role in regulating various physiological processes. It is also involved in several vital functions, such as metabolism, secretion, and storage. It has great capacity to detoxicate toxic substances and synthesize useful principles (Shanani, 1999; Subramoniam and Pushpagandan, 1999; Adewusi and Afolayan, 2010). It helps in the maintenance, performance, and regulating homeostasis of the body. It is involved with almost all the biochemical pathways to growth, fight against disease, nutrient supply, energy provision, and reproduction. In addition, it aids metabolism of carbohydrate, protein and fat, detoxification, secretion of bile, and storage of vitamins (Ahsan et al., 2009). The role played by this organ in the removal of substances from the portal circulation makes it susceptible to first and persistent attack by offending foreign compounds; culminating in liver dysfunction (Bodakhe and Ram, 2007).
Antimicrobial Compounds from Medicinal Plants: Effects on Antibiotic Resistance to Human Pathogens
Megh R. Goyal, Hafiz Ansar Rasul Suleria, Ademola Olabode Ayeleso, T. Jesse Joel, Sujogya Kumar Panda in The Therapeutic Properties of Medicinal Plants, 2019
The classical production of β-lactamase is a typical example of such a mechanism, which precedes the first antibiotic penicillin discovery [16]. They utilize biochemical pathways, such as: Inactivation of drugs with beta-lactamases.Acetylases, adenylases, and phosphorylases.Reduction of drug access to sites of action.Alteration of drug target sites.Bypassing of drug metabolism and developing tolerance.
Hereditary and Metabolic Diseases of the Central Nervous System in Adults
Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw in Hankey's Clinical Neurology, 2020
Acute encephalopathy in neurometabolic disorders variously results from liver failure, hypoglycemia, or direct neurotoxic effects of ammonia (urea cycle disorders), organic acids (organic acidemias), or metal accumulation (Wilson's disease [WD]). In many small molecule intoxication-type disorders, acute symptoms can be triggered by external physiological stressors such as illness, childbirth, surgery, prolonged fasting, high protein intake, or steroid medications. These triggers induce catabolism (breakdown of proteins and other macromolecules), which overwhelms the affected biochemical pathway and leads to the accumulation of metabolic intermediates. Symptoms appear once toxic compounds accumulate to sufficient levels, which may be days or even a week after the insult. For example, encephalopathy after surgery has been reported as the first symptom of disease in many adults with late-onset/partial ornithine transcarbamylase (OTC) deficiency. In this urea cycle disorder, ammonia produced from the breakdown of amino acids is not adequately detoxified to urea, so patients develop hyperammonemic encephalopathy progressing to cerebral edema or strokes. The disease spectrum of OTC deficiency in adults includes individuals whose first ever symptom is fatal postsurgical cerebral edema after age 50 and individuals with recurrent episodes of headache, irritability, and seizure who turn out to have had recurrent hyperammonemia with cortical and subcortical infarcts.4,5
Repair mechanism of Wuwei Fuzheng Yijing formula in di-2-ethylhexyl phthalate-induced sperm DNA fragmentation in mice
Published in Pharmaceutical Biology, 2022
Chenming Zhang, Shiqi Wang, Zulong Wang, Qi Zhang, Rubing Chen, Hao Zhang, Zhong Hua, Sicheng Ma
Our combined transcriptome and proteome analysis found that the repairing effect of WFY on DEHP-induced sperm DNA damage was related to the metabolic pathway and the PI3K/Akt pathway. The metabolic pathway involves many functional activities, and changes in the metabolic pathway have been found in many diseases. The PI3K/Akt pathway is correlated with oxidative damage and DNA integrity. Activation of the PI3K/Akt signalling pathway leads to a direct interaction between phosphorylated MDM2 and p53 degradation. P53 degradation causes p53-dependent DNA damage checkpoint or repair dysfunction and ultimately results in the accumulation of DNA damage in sperm (Xian et al. 2017). Although no other Chinese herbal formulas have been found to repair sperm DNA damage through the PI3K/Akt pathway, some Chinese herbal formulas were able to improve other sperm parameters (such as sperm concentration and motility) through the PI3K/Akt pathway, possibly by promoting spermatogenic cell proliferation and inhibiting apoptosis (Chen et al. 2021).
Pathophysiology of diabetic macular edema – a background for current treatment modalities
Published in Expert Review of Ophthalmology, 2018
Christos Haritoglou, Mathias Maier, Albert Augustin
It is reasonable to approach both, diabetic retinopathy and maculopathy from a biochemical perspective. These disease entities are mainly driven by four biochemical pathways: (a) the PKC pathway, (b) the advanced glycation end products pathway, (c) the polyol pathway, and (d) the hexosamine pathway [19]. The biochemical changes resulting from these pathways finally lead to an enhanced oxidative stress, propagation of inflammatory reactions and vascular dysfunction which the leads to neuronal suffering. In detail, oxidative processes and inflammatory reactions result in upregulation of growth factors and several cytokines. Those are interleukins (ILs), matrix metalloproteinases (MMPs), VEGF-A, angiopoietins, and tumor necrosis factor (TNF). The overexpression of these molecules is responsible for the breakdown of the blood retinal barrier (BRB) and development of DME [20].
Characterisation of seven medications approved for attention-deficit/hyperactivity disorder using in vitro models of hepatic metabolism
Published in Xenobiotica, 2022
Rebecca Law, David Lewis, Daniel Hain, Rachel Daut, Melissa P. DelBello, Jean A. Frazier, Jeffrey H. Newcorn, Erika Nurmi, Elizabeth S. Cogan, Susanne Wagner, Holly Johnson, Jerry Lanchbury
CLD, dAMPH, and AMPH had little to no substrate loss (Figure 1(C–F)). However, appreciable metabolism was observed in the positive controls (Supplemental Table 2), and minor metabolite formation was detected for 4-OH-AMPH, norephedrine, 4-OH-norephedrine, 4-OH-CLD, and 2-[(2,6-Dichlorophenyl)-imino]-imidazolidine-4-one. 4-OH-AMPH peaked at 24 h at 8.74 pmol after AMPH administration, and at 48 h at 6.04 pmol after dAMPH administration. Norephedrine peaked at 2.55 pmol 24 h after AMPH administration (Figure 2(C)) and at 2.32 pmol, 24 h after dAMPH administration (Figure 2(D)). 4-OH-norephedrine was also formed. Phenylacetone, a metabolite within the major metabolic pathway of AMPH, was not detected. Finally, 4-OH-CLD peaked at 48 h at 17.3 pmol (Figure 2(G)) and 2-[(2,6-dichlorophenyl)-imino]-imidazolidine-4-one also formed from CLD. None of the metabolites formed in the absence of cPHHs, indicating some enzymatic metabolism of AMPH, dAMPH, and CLD occurred, albeit negligible.
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