RESUMO
Statins, which are competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, reduce cholesterol blood levels and the risk of developing cardiovascular diseases and their related complications. In addition to this main activity, statins show pleiotropic effects such as antioxidant, anti-inflammatory and antiproliferative properties, with applications in many pathologies. Based on their antiproliferative properties, in vitro and in vivo studies have investigated their effects on various types of cancer (i.e., breast cancer, prostate cancer, colorectal cancer, ovarian cancer, lung cancer) with different genetic and molecular characteristics. Many positive results were obtained, but they were highly dependent on the physiochemical properties of the statins, their dose and treatment period. Combined therapies of statins and cytotoxic drugs have also been tested, and synergistic or additive effects were observed. Moreover, observational studies performed on patients who used statins for different pathologies, revealed that statins reduced the risk of developing various cancers, and improved the outcomes for cancer patients. Currently, there are many ongoing clinical trials aimed at exploring the potential of statins to lower the mortality and the disease-recurrence risk. All these results are the foundation of new treatment directions in cancer therapy.
RESUMO
BACKGROUND Curcumin is an antioxidant that reduces inflammation and pain. This study aimed to assess the effect of pretreatment with naproxen and liposomal curcumin compared with naproxen and curcumin solution on oxidative stress parameters and pain in a rat model of migraine. MATERIAL AND METHODS Sixty-three male Wistar rats included a control group (n=9) and a rat model of migraine (n=54) induced by intraperitoneal injection of nitroglycerin (1 mg/0.1 kg). The rat model group was divided into an untreated control group (n=9), a group pretreated with naproxen alone (2.8 mg/kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (1 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (2 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (1 mg/0.1 kg) (n=9) a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (2 mg/0.1 kg) (n=9). Spectroscopy measured biomarkers of total oxidative status and nociception was tested using an injection of 1% of formalin into the rat paw. RESULTS Expression of biomarkers of oxidative stress and enhanced nociception were significantly increased following pretreatment with combined naproxen and liposomal curcumin compared with curcumin solution or naproxen alone (P<0.001). Combined curcumin solution and naproxen were more effective at a concentration of 2 mg/0.1kg for the first nociceptive phase (P<0.005). CONCLUSIONS In a rat model of migraine, combined therapy with liposomal curcumin and naproxen showed an improved antioxidant effect and anti-nociceptive effect.
Assuntos
Curcumina/farmacologia , Transtornos de Enxaqueca/tratamento farmacológico , Naproxeno/farmacologia , Animais , Antioxidantes/farmacologia , Curcumina/metabolismo , Modelos Animais de Doenças , Quimioterapia Combinada/métodos , Inflamação/tratamento farmacológico , Masculino , Transtornos de Enxaqueca/metabolismo , Naproxeno/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Dor/tratamento farmacológico , Medição da Dor/métodos , Ratos , Ratos WistarRESUMO
Curcumin (CC) is known to have anti-inflammatory and anti-oxidative properties and has already been tested for its efficiency in different diseases including diabetes mellitus (DM). New formulations and route administration were designed to obtain products with higher bioavailability. Our study aimed to test the effect of intraperitoneal (i.p.) administration of liposomal curcumin (lCC) as pre-treatment in streptozotocin(STZ)-induced DM in rats on oxidative stress, liver, and pancreatic functional parameters. Forty-two Wistar-Bratislava rats were randomly divided into six groups (seven animals/group): control (no diabetes), control-STZ (STZ-induced DM -60 mg/100g body weight a single dose intraperitoneal administration, and no CC pre-treatment), two groups with DM and CC pre-treatment (1mg/100g bw-STZ + CC1, 2 mg/100g bw-STZ + CC2), and two groups with DM and lCC pre-treatment (1 mg/100g bw-STZ + lCC1, 2 mg/100g bw-STZ + lCC1). Intraperitoneal administration of Curcumin in diabetic rats showed a significant reduction of nitric oxide, malondialdehyde, total oxidative stress, and catalase for both evaluated formulations (CC and lCC) compared to control group (p < 0.005), with higher efficacy of lCC formulation compared to CC solution (p < 0.002, excepting catalase for STZ + CC2vs. STZ + lCC1when p = 0.0845). The CC and lCC showed hepatoprotective and hypoglycemic effects, a decrease in oxidative stress and improvement in anti-oxidative capacity status against STZ-induced DM in rats (p < 0.002). The lCC also proved better efficacy on MMP-2, and -9 plasma levels as compared to CC (p < 0.003, excepting STZ + CC2 vs. STZ + lCC1 comparison with p = 0.0553). The lCC demonstrated significantly better efficacy as compared to curcumin solution on all serum levels of the investigated markers, sustaining its possible use as adjuvant therapy in DM.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Lipossomos/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Curcumina/administração & dosagem , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Hipoglicemiantes/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Estresse Oxidativo , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Ratos , Ratos WistarRESUMO
Cancer nanotechnology is a new field of interdisciplinary research cutting across biology, chemistry, engineering, and medicine, aiming to lead to major advances in cancer treatment. Over the past several years, solid lipid nanoparticles (SLNs) have attracted the interest of researchers due to their ability to overcome the limitations of classic chemotherapeutics. We reviewed the most recent data on the therapeutic use of SLNs in oncology, presenting their main advantages and disadvantages, along with various production methods and different routes of administration. In accordance with these aspects, the long-term physical stability, the controlled release of the loaded drugs, and the efficient targeted delivery of drugs as methods of surpassing the pharmaceutical limitations of anticancer drugs, natural products and gene therapy have been discussed. In addition, we have also emphasized briefly the crosstalk between SLNs and the new trend in oncology, immunotherapy, as future possible antineoplastic treatment, especially in melanoma. This review highlights the potential of SLNs in providing very positive perspectives for future cancer treatment by improving the efficiency of present chemotherapy and reducing its side effects. SLNs allow targeted delivery of anticancer drugs and could improve the efficiency of current chemotherapy in neoplasia.