Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress. This review updates the research conducted over the past decades into the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and ultimately their correlation with the toxicity and metabolism of APAP. The metabolism of APAP involves various CYP450 enzymes, through which oxidative stress might occur, and such metabolic factors are reviewed within. The therapeutics of a variety of compounds against APAP-induced organ damage based on their anti-oxidative effects is also discussed, in order to further understand the role of oxidative stress in APAP-induced toxicity. This review will throw new light on the critical roles of oxidative stress in APAP-induced toxicity, as well as on the contradictions and blind spots that still exist in the understanding of APAP toxicity, the cellular effects in terms of organ injury and cell signaling pathways, and finally strategies to help remedy such against oxidative damage.

Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro.

The present study reports the antioxidant and membrane protective activities of Calotropis procera aqueous root extract using several in vitro assays along with the determination of phenolic as well as flavonoid contents. Total phenol and flavonoid contents in extract were 15.67 ± 1.52 mg propyl gallate equivalent/g and 1.62 ± 0.05 mg quercetin equivalent/g, respectively. UV-visual spectroscopic scanning of the extract indicated the presence of glycoside-linked tannins or flavonoids. The extract exhibited appreciable reducing power signifying hydrogen donating potential. DPPH radical scavenging assay revealed substantial free radical scavenging activity (42–90%) in the extracts. Concentration dependent response was observed in the metal ion chelating activity (16–95%). Extracts also provided protection against iron induced lipid peroxidation in rat tissue (liver, brain, and kidney) homogenates. Comparatively better protective efficacy against peroxidative damage was observed in liver (71%) followed by kidney (65%) and brain (60%) tissues. Positive correlation was observed between DPPH free radical scavenging activity and reducing power of extract. Similarly strong positive correlation was observed between metal ion chelating ability and percentage lipid peroxidation inhibition in different tissues. The study demonstrated considerable protective efficacy in C. procera root aqueous extracts against free radical and metal ion mediated oxidative damage.

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Calotropis procera Root Extract Has the Capability to Combat Free Radical Mediated Damage

Flavonoids and other polyphenols play a protective role in liver diseases and possess a high antioxidant capacity. To compare and evaluate the antioxidant and hepatotoprotective activities of 4 deserts plants, Fagonia indica Burm. f., Calotropis procera R.Br., Zygophylum hamiense Schweinf. and Salsola imbricata Forssk. in correlation to their composition especially their phenolic content. The influence of extracting solvent on total phenolic and flavonoidal contents was assessed spectrophotometrically. The flavonoid and other polyphenolic components of the methanol extracts were analyzed by RP-HPLC. DPPH radical scavenging potential of the different extracts was estimated. The hepatoprotective and antioxidant activities of the extracts against CCl4-induced hepatotoxicity in mice were evaluated. The flavonol quercitrin and rosmarinic acid were major in the F. indica, C. procera and S. imbricata samples, while rutin prevailed in that of Z. hamiense. The ethanolic and methanolic extracts showed noticeable DPPH radical-scavenging activity as compared to ascorbic acid. Assessment of liver enzymes revealed that oral administration of the extracts did not show any evidence of hepatotoxicity. Moreover, protection against CCl4-induced liver damage was evident upon administration of three plants extracts namely, F. indica, C. procera and S. imbricata.
 Overall, hepatotoxicity induced by CCl4 was effectively prevented by the three plants extracts through scavenging of free radicals and by boosting the antioxidant capacity of the liver. The protective effect of the plants could be attributed to their high quercitrin and rosmarinic acid contents.

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Impact of phenolic composition on hepatoprotective and antioxidant effects of four desert medicinal plants

The cytotoxic potential of stem organic extracts from Calotropis procera (Asclepiadaceae) was firstly evaluated against cancer cell lines by MTT assay. Subsequently, samples considered cytotoxic were tested for antimitotic activity on sea urchin egg development and for in vivo antiproliferative activity in mice bearing Sarcoma 180 tumor. Among the five extracts (hexane, dichloromethane, ethyl acetate, acetone and methanol), ethyl acetate and acetone extracts displayed higher cytotoxic potential against tumor cells, with IC50 ranging from 0.8 to 4.4 microg/mL, while methanolic extract was weakly cytotoxic. Cytotoxic extracts also exhibited cell division inhibition capacity by antimitotic assay, revealing IC50 values lower than 5 microg/mL. In the in vivo antitumor assessments, ethyl acetate- and acetone-treated animals showed tumor growth inhibition ratios of 64.3 and 53.1%, respectively, with reversible toxic effects on liver and kidneys. Further studies are in progress in order to identify C. procera cytotoxic compound(s) and to understand the mechanism of action responsible for this tumor-decreasing potential.

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Absar Ahmed Quereshi

Papers

Hepatoprotective activity of Calotropis procera flowers against paracetamol-induced hepatic injury in rats