Preclinical study comparing the antidotal effect of clonidine with atropine for the treatment of acute malathion poisoning in the albino rats

Background: In developing countries 2–3 million people are acutely poisoned by organophosphorus (OP) pesticides every year. There is a pressing need for new affordable antidotes and in this context clonidine which has central effect (α2 agonist) has been evaluated in the albino rats presenting with signs or symptoms of acute malathion poisoning. And compared with atropine for the acte malathion poisoning in albino rats.Methods: This was a preclinical study conducted on albino rats of either sex weighing 100-150 grams were randomly divided into 4 groups (6/group). Malathion was given at the lethal dose of 54 mg/kg body weight (BW) by gavage to each group. Group 1: normal saline intraperioneal (i.p). Group 2: Post treated with atropine 1.5 mg/kg BW (i.p). Group 3: Pre treated with clonidine 1mg/ kg BW (i.p), 10 minutes priore malathion. Group 4: Pre treated with clonidine and post treated with atropine. The above groups were observed for straub tail, muscle fasciculation, piloerection, lacrimation, defecation/ urination; salivation, tremors, gasping and convulsion and were recorded at time 0, 15, 30, 45 and 60 minutes after poisoning. The latency of onset of tremors, loss of righting reflex and tremors were recorded. Results were presented as percentage occurrence and Mean ± SEM. Repeated measure one way ANOVA and Fisher’s Least Significant Difference post hoc test for comparison between groups. P-value of 0.05 or less was considered for statistical significance.Results: The central effects namely straubs tail and whole body tremors are significantly improved compared to control and atropine with clonidine group (p<0.05). However convulsion shows improve in atropine alone and atropine with clonidine groups. The overall survival time has significantly increased compared to control and atropine and atropine with clonidine (P<0.05).Clonidine has not shown any effect on survival time.Conclusions: Clonidine has some central protective effect in malathion poisoning. And it has not shown any effect on survival time. This issue needs further controlled studies

Botany, chemistry, and pharmaceutical significance of Sida cordifolia: a traditional medicinal plant

Sida cordifolia Linn. belonging to the family, Malvaceae has been widely employed in traditional medications in many parts of the world including India, Brazil, and other Asian and African countries. The plant is extensively used in the Ayurvedic medicine preparation. There are more than 200 plant species within the genus Sida, which are distributed predominantly in the tropical regions. The correct taxonomic identification is a major concern due to the fact that S. cordifolia looks morphologically similar with its related species. It possesses activity against various human ailments, including cancer, asthma, cough, diarrhea, malaria, gonorrhea, tuberculosis, obesity, ulcer, Parkinson’s disease, urinary infections, and many others. The medical importance of this plant is mainly correlated to the occurrence of diverse biologically active phytochemical compounds such as alkaloids, flavonoids, and steroids. The major compounds include β-phenylamines, 2-carboxylated tryptamines, quinazoline, quinoline, indole, ephedrine, vasicinone, 5-3-isoprenyl flavone, 5,7-dihydroxy-3-isoprenyl flavone, and 6-(isoprenyl)- 3-methoxy- 8-C-β-D-glucosyl-kaempferol 3-O-β-D-glucosyl[1–4]-α-D-glucoside. The literature survey reveals that most of the pharmacological investigations on S. cordifolia are limited to crude plant extracts and few isolated pure compounds. Therefore, there is a need to evaluate many other unexplored bioactive phytoconstituents with evidences so as to justify the traditional usages of S. cordifolia. Furthermore, detailed studies on the action of mechanisms of these isolated compounds supported by clinical research are necessary for validating their application in contemporary medicines. The aim of the present chapter is to provide a detailed information on the ethnobotanical, phytochemical, and pharmacological aspects of S. cordifolia

Probing p300/CBP associated Factor (PCAF)-dependent pathways with a small molecule inhibitor

PCAF (KAT2B) belongs to the GNAT family of lysine acetyltransferases (KAT) and specifically acetylates the histone H3K9 residue and several nonhistone proteins. PCAF is also a transcriptional coactivator. Due to the lack of a PCAF KAT-specific small molecule inhibitor, the exclusive role of the acetyltransferase activity of PCAF is not well understood. Here, we report that a natural compound of the hydroxybenzoquinone class, embelin, specifically inhibits H3Lys9 acetylation in mice and inhibits recombinant PCAF-mediated acetylation with near complete specificity in vitro. Furthermore, using embelin, we have identified the gene networks that are regulated by PCAF during muscle differentiation, further highlighting the broader regulatory functions of PCAF in muscle differentiation in addition to the regulation via MyoD acetylation

Probing p300/CBP Associated Factor (PCAF)-Dependent Pathways with a Small Molecule Inhibitor

PCAF (KAT2B) belongs to the GNAT family of lysine acetyltransferases (KAT) and specifically acetylates the histone H3K9 residue and several nonhistone proteins. PCAF is also a transcriptional coactivator. Due to the lack of a PCAF KAT-specific small molecule inhibitor, the exclusive role of the acetyltransferase activity of PCAF is not well understood. Here, we report that a natural compound of the hydroxybenzoquinone class, embelin, specifically inhibits H3Lys9 acetylation in mice and inhibits recombinant PCAF-mediated acetylation with near complete specificity <i>in vitro</i>. Furthermore, using embelin, we have identified the gene networks that are regulated by PCAF during muscle differentiation, further highlighting the broader regulatory functions of PCAF in muscle differentiation in addition to the regulation via MyoD acetylation

Probing p300/CBP Associated Factor (PCAF)-Dependent Pathways with a Small Molecule Inhibitor

PCAF (KAT2B) belongs to the GNAT family of lysine acetyltransferases (KAT) and specifically acetylates the histone H3K9 residue and several nonhistone proteins. PCAF is also a transcriptional coactivator. Due to the lack of a PCAF KAT-specific small molecule inhibitor, the exclusive role of the acetyltransferase activity of PCAF is not well understood. Here, we report that a natural compound of the hydroxybenzoquinone class, embelin, specifically inhibits H3Lys9 acetylation in mice and inhibits recombinant PCAF-mediated acetylation with near complete specificity <i>in vitro</i>. Furthermore, using embelin, we have identified the gene networks that are regulated by PCAF during muscle differentiation, further highlighting the broader regulatory functions of PCAF in muscle differentiation in addition to the regulation via MyoD acetylation