Paracetamol-induced changes of haematobiochemical and oxidative stress parameters in rat blood: Protective role of vitamin C and β-glucan

Fahim

Oxidative Medicine and Cellular Longevity

et al. 2019

N-Acetyl-p-aminophenol (APAP) or acetaminophen is the most common drug ingredient worldwide. It is found in more than 600 different over-the-counter and prescription medicines. Its long-term and overdose use is highly toxic and may result in liver injury. Thus, this study was designed to assess the preventive effects and to suggest the mechanisms of action of the navel orange peel hydroethanolic extract, naringin, and naringenin in APAP-induced hepatotoxicity in male Wistar rats. APAP was administered to male Wistar rats at a dose level of 0.5 g/kg body weight (b.w.) by oral gavage every other day for 4 weeks. APAP-administered rats were treated with the navel orange peel hydroethanolic extract (50 mg/kg b.w.), naringin (20 mg/kg b.w.), and naringenin (20 mg/kg b.w.) by oral gavage every other day during the same period of APAP administration. The treatments of APAP-administered rats with the peel extract, naringin, and naringenin produced a significant decrease in the elevated serum AST, ALT, ALP, LDH, and GGT activities as well as total bilirubin and TNF-α levels while they induced a significant increase in the lowered serum albumin and IL-4 levels. The treatments also resulted in a significant decrease in the elevated liver lipid peroxidation and enhanced the liver GSH content and SOD, GST, and GPx activities as compared with APAP-administered control; the peel extract was the most potent in improving the liver LPO, GSH content, and GPx activity. In addition, the three treatments significantly downregulated the elevated hepatic proapoptotic mediators p53, Bax, and caspase-3 and significantly upregulated the suppressed antiapoptotic protein, Bcl-2, in APAP-administered rats. In association, the treatments markedly amended the APAP-induced liver histopathological deteriorations that include hepatocyte steatosis, cytoplasmic vacuolization, hydropic degeneration, and necrosis together with mononuclear leucocytic and fibroblastic inflammatory cells’ infiltration. In conclusion, the navel orange peel hydroethanolic extract, naringin, and naringenin may exert their hepatopreventive effects in APAP-administered rats via enhancement of the antioxidant defense system and suppression of inflammation and apoptosis.

Section: Discussionsupporting

confidence: 78%

The Preventive Effects and the Mechanisms of Action of Navel Orange Peel Hydroethanolic Extract, Naringin, and Naringenin in N-Acetyl-p-aminophenol-Induced Liver Injury in Wistar Rats

Fahim

Oxidative Medicine and Cellular Longevity

et al. 2019

“…In contrast to the pattern of serum total bilirubin level, the results of a research by Okokon et al [83] show that NAPAP-administered rats had significantly lower blood albumin levels. This drop in albumin levels in rats receiving NAPAP may be brought about by necrosis, apoptosis, and liver cell degeneration, which result in a reduction in the number of cells producing albumin [84]. Histological findings showing the presence of cytoplasmic vacuolization of hepatocytes, focal hepatic necrosis associated with inflammatory cell infiltration, numerous apoptotic cells, portal infiltration with inflammatory cells, and congestion of the central vein support the impairment in liver function parameters in serum, including ALAT, ASAT, AP, GT, and LDH activities, as well as total bilirubin and albumin levels, caused by NAPAP administration.…”

Section: Discussionmentioning

confidence: 99%

Preventive Effects of Mandarin Fruit Peel Hydroethanolic Extract, Hesperidin, and Quercetin on Acetaminophen-Induced Hepatonephrotoxicity in Wistar Rats

Eldin

Fahim

Oxidative Medicine and Cellular Longevity

et al. 2022

Acetaminophen, also known as N-acetyl-para-aminophenol (NAPAP), is a traditional antipyretic and analgesic that is used extensively around the world to treat colds and fevers. However, a NAPAP excess causes rapid, severe liver and kidney damage. The goal of the study was to examine the protective effects and determine the mechanisms of action of MPHE, hesperidin, and quercetin in NAPAP-induced hepatorenal damage in Wistar rats. Male Wistar rats received a 0.5 g/kg oral supplement of NAPAP every other day for a period of four weeks. During the same period of NAPAP supplementation, MPHE (50 mg/kg), quercetin (20 mg/kg), and hesperidin (20 mg/kg) were administered to rats receiving NAPAP. MPHE, quercetin, and hesperidin treatments significantly improved liver function in NAPAP-supplemented rats. The high serum levels of aminotransferases, alkaline phosphatase, lactate dehydrogenase, and γ-glutamyl transferase as well as total bilirubin were significantly reduced, while the levels of suppressed serum albumin were significantly increased, demonstrating this improvement. Treatments utilizing these natural substances significantly enhanced kidney function as seen by a considerable decline in the increased blood levels of urea, uric acid, and creatinine. Additionally, the injection of MPHE, hesperidin, and quercetin resulted in a decrease in the quantity of lipid peroxides while increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase in the liver and kidneys. The treatments markedly abated the NAPAP-induced liver and kidney histological perturbations and reduced the NAPAP-induced serum tumor necrosis factor-α level and liver and kidney proapoptotic protein 53 and caspase 3 expressions. Otherwise, serum interleukin-4 level significantly increased by treatments. The MPHE, hesperidin, and quercetin treatments resulted in marked decrease in liver and kidney histopathological scores including inflammation, necrosis, apoptosis, and congestion. In conclusion, the MPHE, quercetin, and hesperidin may induce hepatonephropreventive impacts in NAPAP-supplemented rats via enhancing the antioxidant defense system, anti-inflammatory activity, and antiapoptotic action.

“…Further, paracetamol is scrutinized as a derivative of para-aminophenol class of NSAIDs and broadly used in analgo-antipyretic purposes without medical prescription especially in childhood (Aghababian, 2010;Hamza & Al-Harbi, 2015;Matić et al, 2016). The major goal of the current work was to explore the immunological and biochemical changes in mice after administration with repeated doses of Diclo, Ibu, and Para for 1 month.…”

Section: Discussionmentioning

confidence: 99%

Adverse effects induced by diclofenac, ibuprofen, and paracetamol toxicity on immunological and biochemical parameters in Swiss albino mice

Gomaa

2018

JoBAZ

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally used to reduce pain in different diseases acting as anti-inflammatory, antipyretic, and analgesic. Paracetamol is a nonprescription drug extremely used for antipyresis and analgesia. In spite of their beneficial effects, NSAIDs have been notified to be linked with some adverse effects. The present study was conducted to elucidate the comparative biochemical and immunological changes in mice treated with diclofenac (Diclo), ibuprofen (Ibu), or paracetamol (Para). Methods: Swiss albino mice were divided uniformly into seven different groups. Mice were intraperitoneally (i.p.) administered with Diclo (7.4 and 14.8 mg/kg), Ibu (60 and 120 mg/kg), and Para (36.7 and 73.4 mg/kg) daily for 1 month against saline-treated mice served as control. Blood samples were collected, and the assessments of some biochemical and immunological markers were measured.