Type 2 diabetes mellitus (DM2) is a metabolic disorder characterized by chronic hyperglycemia associated with low insulin production and/or insulin resistance. A high-fat diet (HFD) combined with a low dose of streptozotocin (STZ) in an animal model produces a disease that mimics type 2 diabetes mellitus in humans. However, there is wide variation in the methods of inducing diabetes in terms of the dose of STZ, the duration of the induction period, and the composition of the diet used, all of which could result in biological responses that are not typical of the disease. This review aims to investigate the characteristics of an experimental model of type 2 diabetes mellitus by combining a high-fat diet with low doses of streptozotocin in Wistar rats. This is an integrative review conducted by searching in the Medline, Lilacs, and Embase databases using the keywords “type 2 diabetes mellitus”, “high-fat diet”, “streptozotocin” and “Wistar rats”. Articles published in English between 2018 and 2025 were included. The induction of DM2 in young male rats with a high-fat HFD for a period of at least 3 weeks followed by a low dose of STZ resulted in metabolic, histological, inflammatory, and oxidative changes, and alterations in the signaling pathways of glycemic and lipid metabolism in different tissues, replicating the characteristics observed in humans. HFD-fed + STZ-induced Wistar rats constitute an effective animal model for studying DM2.
Hemorrhagic cystitis is the main adverse effect associated with the clinical use of oxazaphosphorine, resulting in increased oxidative stress and proinflammatory cytokines, which culminate in injury of the bladder tissue. The aim of this study was to evaluate the protective effect of isopropyl gallate (IPG) against ifosfamide (IFOS)-induced hemorrhagic cystitis in mice. The induction of the hemorrhagic cystitis model was carried out using a single dose of IFOS (400 mg/kg, i.p.) four hours after oral pretreatment with IPG (6.25, 12.5, 25, and 50 mg/kg) or saline (vehicle). Mesna (positive control; 80 mg/kg, i.p.) was administered four hours before and eight hours after induction of cystitis. In the present study, IPG 25 mg/kg significantly decreased edema and hemorrhage, with a reduction of the bladder wet weight (36.86%), hemoglobin content (54.55%), and peritoneal vascular permeability (42.94%) in urinary bladders of mice. Interestingly, IPG increased SOD activity (89.27%) and reduced MDA levels (35.53%), as well as displayed anti-inflammatory activity by decreasing TNF-α (88.77%), IL-1β (62.87%), and C-reactive protein (56.41%) levels. Our findings demonstrate that IPG has a substantial protective role against IFOS-induced hemorrhagic cystitis in mice by enhancing antioxidant activity and proinflammatory mechanisms. Thus, IPG represents a promising co-adjuvant agent in oxazaphosphorine-based chemotherapy treatments.
Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12–39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.
Background: Neuropathic pain can be triggered by chemotherapy drugs such as paclitaxel (PTX). Management of pain is limited by drugs’ ineffectiveness and adverse effects. Isopulegol (ISO) is a monoterpene present in the essential oils of several aromatic plants and has promising pharmacological activities. Objectives: to evaluate the antinociceptive activity of ISO in a PTX-induced neuropathic pain model. Methods: the toxicity of ISO was evaluated in healthy and cancerous cells. Behavioral assessments were performed using the von Frey and acetone tests. We investigated the involvement of the GABAergic pathway, NMDA, TNF-α, and the release of GABA and glutamate in the presence of ISO. Results: ISO showed little or no cytotoxicity in U87 and MDA-MB-231 cells. In both acute and subacute treatment, ISO at doses of 25, 50, and 100 mg/kg (* p < 0.05) increased the mechanical nociceptive threshold of neuropathic animals compared to the control group and reduced thermal sensitivity. Its action was reversed by pre-treatment with flumazenil and potentiated by the NMDA antagonist, MK-801. TNF-α and glutamate levels were reduced and GABA release was increased in the tests carried out. Conclusions: ISO shows low toxicity in neuronal cells and its association with PTX generated synergism in its cytotoxic action. The antinociceptive effect of ISO is due to activation of GABA and antagonism of NMDA receptors and involves the stabilization of neuronal plasma membranes leading to an imbalance in the release of neurotransmitters, favoring GABA-mediated inhibition over glutamatergic excitation.
Introduction: Neuropathy caused by chemotherapy, a dose-limiting neurotoxic side effect, often leads to treatment discontinuation. About 30 to 70% of patients treated with paclitaxel experience peripheral neuropathy due to the drug combination and dosage. Given the significant prevalence of neuropathy in individuals who have undergone chemotherapy treatments and the growing need for new therapeutic approaches, including those based on natural resources, it is imperative to investigate substances capable of mitigating this adverse effect. Method: Natural plant compounds are often used to treat various pathological conditions due to superior treatment options and minimal side effects. Rose oxide (RO), monoterpenes present in several essential oils, have demonstrated anti-inflammatory activity by inhibiting IL-1β production and leukocyte migration. Therefore, the present study aimed to investigate the effect of rose oxide in its free form on animal models of neuropathic pain induced by antineoplastics in rats. Neuropathic pain was induced by paclitaxel at a dose of 20 mg/kg i.p. for four consecutive days and treated with rose oxide at doses of 12.5, 25, and 50 mg/kg and after this period, behavioral analyzes (von Frey mechanical allodynia, acetone test and open field), biochemical, hematological and assessment of oxidative stress (malondialdehyde levels). The results suggested that rose oxide has antinociceptive activity in animal models of antineoplastic-induced neuropathic pain in rats. Results: Furthermore, treatment with rose oxide did not show significant adverse effects on biochemical and hematological parameters, with the exception of the 12.5 mg/kg dose of RO affected creatinine levels and all doses of TGP, while the highest dose (50 mg/kg) caused changes in total proteins and albumin, suggesting a more binding strong with plasma proteins. Finally, treatment with RO 25 mg/kg significantly altered malondialdehyde (MDA) levels. Conclusion: These results suggest that the use of rose oxide in its free form may be a promising option for the treatment of antineoplastic-induced neuropathic pain in humans. However, further studies are needed to confirm these findings and evaluate safety and efficacy.
2 September 2019 in Research, Society and Development
A dengue é um problema crescente de saúde pública e tem sido negligenciada ultimamente apesar de ser a doença arboviral mais prevalente no mundo. Esse estudo tem como objetivo descrever os aspectos epidemiológicos da dengue no estado da Paraíba, Nordeste do Brasil, de 2007 a 2012. Os dados foram extraídos de relatórios clínicos do Sistema Nacional de Agravos de Notificação (SINAN) do Brasil fornecidos pelos pelo departamento de informática do SUS DATASUS do Ministério da saúde. Realizou-se uma análise descritiva do número de casos notificados da dengue, segundo ano, raça idade, sexo e os agravos dos casos. De 2007 a 2012 foram notificados 45231 casos suspeitos de dengue. Os anos com altos índices epidêmicos foram: 2011 2007 e 2012 em ordem decrescente. Houve um declínio progressivo da incidência da dengue nos períodos de 2008 a 2010. Esse estudo mostrou o predomínio dos casos em femininas, pardas, com faixa etária entre 20 a 39 anos Em 33 casos o óbito decorreu de fenômenos hemorrágicos e outras complicações, contudo, os 8 casos de óbito foram por causas diferentes. A dengue permanece como importante problema de saúde, com casos graves e alta letalidade. Diante disso, é necessário enfatizar que as políticas públicas de saúde devem adotar e manter ações preventivas por meio de educação em saúde, saneamento básico, boas condições de habitação.