Molecular and Antioxidant Characterization of Opuntia robusta Fruit Extract and Its Protective Effect against Diclofenac-Induced Acute Liver Injury in an In Vivo Rat Model.

A molecular characterization of the main phytochemicals and antioxidant activity of Opuntia robusta (OR) fruit extract was carried out, as well as an evaluation of its hepatoprotective effect against diclofenac (DF)-induced acute liver injury was evaluated. Phenols, flavonoids and betalains were quantified, and antioxidant characterization was performed by means of the ABTS•+, DPPH and FRAP assays. UPLC-QTOF-MS/MS was used to identify the main biocompounds present in OR fruit extract was carried out via. In the in vivo model, groups of rats were treated prophylactically with the OR fruit extract, betanin and N-acteylcysteine followed by a single dose of DF. Biochemical markers of oxidative stress (MDA and GSH) and relative gene expression of the inducible antioxidant response (Nrf2, Sod2, Hmox1, Nqo1 and Gclc), cell death (Casp3) and DNA repair (Gadd45a) were analyzed. Western blot analysis was performed to measure protein levels of Nrf2 and immunohistochemical analysis was used to assess caspase-3 activity in the experimental groups. In our study, the OR fruit extract showed strong antioxidant and cytoprotective capacity due to the presence of bioactive compounds, such as betalain and phenols. We conclude that OR fruit extract or selected components can be used clinically to support patients with acute liver injury.

Hepatoprotective Effect of Opuntia robusta Fruit Biocomponents in a Rat Model of Thioacetamide-Induced Liver Fibrosis.

Liver fibrosis is a chronic disease associated with oxidative stress that has a great impact on the population mortality. Due to their antioxidant capacity, we evaluated the protective effect of Opuntia robusta fruit (Or) on liver fibrosis. A nutraceutical characterization of Or was performed and a model of fibrosis was induced with thioacetamide (TAA) in Wistar rats. Aminotransferases, reduced glutathione (GSH) and histopathology were evaluated. Or contained 436.5 ± 57 mg of Betacyanins equivalents/L., 793 mg of catechin equivalents (CAE)/100 g for flavonoids, 1118 mg of gallic acid equivalents (GAE)/100 g for total phenols, 141.14 mg/100 g for vitamin C and 429.9 µg/100 g for vitamin E. The antioxidant capacity of Or was: 2.27 mmol of Trolox® equivalents (TE)/L (DPPH), 62.2 ± 5.0 µmol TE/g (ABTS•+), 80.2 ± 11.7 µmol TE/g (FRAP), 247.9 ± 15.6 µmol TE/g (AAPH) and 15.0% of H2O2 elimination. An increase (p < 0.05) of aminotransferases and a decrease (p < 0.05) of hepatic GSH was observed in the TAA group compared to the control and the concomitant groups. Histopathology showed changes in the normal architecture of the liver treated with TAA compared to the concomitant treatments. Or contains bioactive components with antioxidant capacity, which can reduce fibrotic liver damage.

Betacyanins, major components in Opuntia red-purple fruits, protect against acetaminophen-induced acute liver failure.

Acetaminophen (APAP) misuse or overdose is the most important cause of drug-induced acute liver failure. Overdoses of acetaminophen induce oxidative stress and liver injury by the electrophilic metabolite N-acetyl-p-benzoquinone imine (NAPQI). Plant-based medicine has been used for centuries against diseases or intoxications due to their biological activities. The aim of this study was to evaluate the therapeutic value of Opuntia robusta and Opuntia streptacantha fruit extracts against acetaminophen-induced liver damage and to identify the major biocomponents on them. Opuntia fruit extracts were obtained by peeling and squeezing each specie, followed by lyophilization. HPLC was used to characterize the extracts. The effect of the extracts against acetaminophen-induced acute liver injury was evaluated both in vivo and in vitro using biochemical, molecular and histological determinations. The results showed that betacyanins are the main components in the analyzed Opuntia fruit extracts, with betanin as the highest concentration. Therapeutic treatments with Opuntia extracts reduced biochemical, molecular and histological markers of liver (in vivo) and hepatocyte (in vitro) injury. Opuntia extracts reduced the APAP-increased expression of the stress-related gene Gadd45b. Furthermore, Opuntia extracts exerted diverse effects on the antioxidant related genes Sod2, Gclc and Hmox1, independent of their ROS-scavenging ability. Therefore, betacyanins as betanin from Opuntia robusta and Opuntia streptacantha fruits are promising nutraceutical compounds against oxidative liver damage.

Natural Dietary Pigments: Potential Mediators against Hepatic Damage Induced by Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs.

Over-the-counter (OTC) analgesics are among the most widely prescribed and purchased drugs around the world. Most analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The hepatocytes are responsible for drug metabolism and detoxification. Cytochrome P450 enzymes are phase I enzymes expressed mainly in hepatocytes and they account for ≈75% of the metabolism of clinically used drugs and other xenobiotics. These metabolic reactions eliminate potentially toxic compounds but, paradoxically, also result in the generation of toxic or carcinogenic metabolites. Cumulative or overdoses of OTC analgesic drugs can induce acute liver failure (ALF) either directly or indirectly after their biotransformation. ALF is the result of massive death of hepatocytes induced by oxidative stress. There is an increased interest in the use of natural dietary products as nutritional supplements and/or medications to prevent or cure many diseases. The therapeutic activity of natural products may be associated with their antioxidant capacity, although additional mechanisms may also play a role (e.g., anti-inflammatory actions). Dietary antioxidants such as flavonoids, betalains and carotenoids play a preventive role against OTC analgesics-induced ALF. In this review, we will summarize the pathobiology of OTC analgesic-induced ALF and the use of natural pigments in its prevention and therapy.

Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage.

Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-L-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800mg/kg/day, orally) were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally). Rat hepatocyte cultures were exposed to 20mmol/LAPAP, and necrosis was assessed by LDH leakage. Opuntia robusta had significantly higher levels of antioxidants than Opuntia streptacantha. Both extracts significantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts significantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF.