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.

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.

Background: Patients with cervical cancer (CC) receiving chemotherapy and radiotherapy have several gastrointestinal adverse effects. Objective: To evaluate the effect of dietary symbiotic supplementation on fecal calprotectin, bacterial DNA levels, and gastrointestinal adverse effects in patients with CC. Methods: Clinical, controlled, randomized, double-blind trial. Patients consumed symbiotics or placebo three times a day for 7 weeks. Fecal calprotectin was assessed by Elisa method. DNA from probiotic and pathogenic bacteria were determined by quantitative real-time polymerase chain reaction. Diarrheal evacuations were evaluated with the Bristol scale and nausea and vomiting were measured using the scale of the National Institute of Cancerology of the United States. Results: Fecal calprotectin concentration was lower in the symbiotic group compared to the control group (p <0.001). The concentrations and total proportions of the probiotic and pathogenic bacteria were similar in both groups. Nausea cases significantly diminished in both groups (p <0.001) at the end of the trial. Furthermore, the symbiotic group had a statistically significant decrease in the frequency and intensity of vomiting when compared to the control group (p <0.001). Conclusions: The symbiotic treatment decreases significantly the fecal calprotectin levels and the frequency and intensity of vomiting in patients with CC. KEYWORDS: faecal calprotectin, cervical cancer, symbiotic, qPCR.

The aim of this study was to detect and analyze Adverse Drug Reactions (ADRs) through Intensive Pharmacovigilance (IPV) in hospitalized pediatric patients to improve drug safety. A prospective 6-month cross-sectional study was performed in the pediatric service of a regional hospital in Mexico in order to assess hospitalized children from 1 day to 18 years old. The inclusion criteria were: both genders, all hospitalization causes, and at least one prescribed medication (indistinct drug group). Notifications were performed through medical visits, phone calls, or spontaneous reports. ADR suspicions were assessed with severity scales: Naranjo algorithm, Schumock & Thornton and Hartwig and Siegel. From a total of 1083 hospital admissions, 19 ADRs were recorded. The average age of patients in years was 7.2 (±5.9). The causality assessment in this study showed that most of the ADRs were probable (68.4%) and 4 certain (8.2%); causality was mainly attributed to antibiotics (AB) and an antiepileptic drug. We found a relationship of AB with ADRs (p < 0.05) with an increased risk at the third day of prescription (p < 0.05). The average severity was level 2 and 21% were classified as “preventable”. Lastly, an increase in hospital stay associated with ADRs (p < 0.05) and with concomitant medications (p < 0.05), was also found. The most severe ADRs were hemolysis and toxic epidermal necrolysis. IPV was an effective tool for ADR prevention, detection, and treatment in hospitalized patients. The intensive monitoring approach in pharmacovigilance amplifies ADR detection and this translates into the improvement of drug safety in children.

Cancer induced by a viral infection is among the leading causes of cancer. Hepatitis C Virus (HCV) is a hepatotropic oncogenic positive-sense RNA virus that leads to chronic infection, exposing the liver to a continuous process of damage and regeneration and promoting hepatocarcinogenesis. The virus promotes the development of carcinogenesis through indirect and direct molecular mechanisms such as chronic inflammation, oxidative stress, steatosis, genetic alterations, epithelial-mesenchymal transition, proliferation, and apoptosis, among others. Recently, direct-acting antivirals (DAAs) showed sustained virologic response in 95% of cases. Nevertheless, patients treated with DAAs have reported an unexpected increase in the early incidence of Hepatocellular carcinoma (HCC). Studies suggest that HCV induces epigenetic regulation through non-coding RNAs, DNA methylation, and chromatin remodeling, which modify gene expressions and induce genomic instability related to HCC development that persists with the infection’s clearance. The need for a better understanding of the molecular mechanisms associated with the development of carcinogenesis is evident. The aim of this review was to unravel the molecular pathways involved in the development of carcinogenesis before, during, and after the viral infection’s resolution, and how these pathways were regulated by the virus, to find control points that can be used as potential therapeutic targets.

Aminoguanidine (AG) inhibits advanced glycation end products (AGEs) and advanced oxidation protein products (AOPP) accumulated as a result of excessive oxidative stress in diabetes. However, the molecular mechanism by which AG reduces AGE‑associated damage in diabetes is not well understood. Thus, we investigated whether AG supplementation mitigates oxidative‑associated cardiac fibrosis in rats with type 2 diabetes mellitus (T2DM). Forty‑five male Wistar rats were divided into three groups: Control, T2DM and T2DM+AG. Rats were fed with a high‑fat, high‑carbohydrate diet (HFCD) for 2 weeks and rendered diabetic using low‑dose streptozotocin (STZ) (20 mg/kg), and one group was treated with AG (20 mg/kg) up to 25 weeks. In vitro experiments were performed in primary rat myofibroblasts to confirm the antioxidant and antifibrotic effects of AG and to determine if blocking the receptor for AGEs (RAGE) prevents the fibrogenic response in myofibroblasts. Diabetic rats exhibited an increase in cardiac fibrosis resulting from HFCD and STZ injections. By contrast, AG treatment significantly reduced cardiac fibrosis, α‑smooth muscle actin (αSMA) and oxidative‑associated Nox4 and Nos2 mRNA expression. In vitro challenge of myofibroblasts with AG under T2DM conditions reduced intra‑ and extracellular collagen type I expression and Pdgfb, Tgfβ1 and Col1a1 mRNAs, albeit with similar expression of Tnfα and Il6 mRNAs. This was accompanied by reduced phosphorylation of ERK1/2 and SMAD2/3 but not of AKT1/2/3 and STAT pathways. RAGE blockade further attenuated collagen type I expression in AG‑treated myofibroblasts. Thus, AG reduces oxidative stress‑associated cardiac fibrosis by reducing pERK1/2, pSMAD2/3 and collagen type I expression via AGE/RAGE signaling in T2DM.