RESUMEN
Curcumin is known to have immunomodulatory potential in addition to anti-oxidant, anti-inflammatory and anti-carcinogenic effects. The aim of the present study is to investigate the therapeutic effects of curcumin on immune-mediated renal disease in an anti-glomerular basement membrane (GBM) model (representing acute kidney Injury, AKI) and murine lupus model (representing chronic kidney disease, CKD). In the AKI model, female anti-GBM 129/svj mice were administered with curcumin right before disease induction. In the CKD model, female MRL.lpr mice at the age of 8-10 weeks old were treated with curcumin or placebo via oral gavage daily for two months. After treatment, serum autoantibody levels, splenomegaly and spleen cellularity were reduced in murine lupus. Collectively, curcumin ameliorated kidney disease in the two mouse models with either acute or chronic nephritis, as marked by reduced proteinuria, blood urea nitrogen, glomerulonephritis, crescent formation, tubule-interstitial disease, and renal infiltration by lymphocytes. In addition, curcumin treatment reduced activation of the NFkB, MAPK, AKT and pBAD pathways either systemically, or within the inflamed kidneys. These findings suggest that natural food supplements could become an alternative approach to ameliorating immune-mediated kidney diseases.
Asunto(s)
Membrana Basal/efectos de los fármacos , Curcumina/farmacología , Glomérulos Renales/efectos de los fármacos , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/prevención & control , Animales , Antiinflamatorios/farmacología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes , Modelos Animales de Enfermedad , Femenino , Glomerulonefritis/tratamiento farmacológico , Riñón/metabolismo , Ratones , Ratones Endogámicos MRL lpr , Proteinuria/tratamiento farmacológico , Transducción de Señal , Bazo/metabolismo , EsplenomegaliaRESUMEN
According to the National Diabetes Statistics Report (2017) by Centers for Disease Control and Prevention (CDC), 9.4% of the US population, approximately 30.3 million people had diabetes while 84.1 million had pre-diabetes as of 2015. In addition to lifestyle changes, the American Diabetes Association recommends metformin as the first-line treatment for type 2 diabetes. Hence, not surprisingly, metformin is a commonly prescribed medication by most healthcare providers in all clinical settings. As a result, it remains essential that all medical professionals be aware of any adverse effects as a result of metformin therapy, no matter how uncommon. We present the case of a 42-year-old lady with type 2 diabetes mellitus who required initial admission to intensive care unit (ICU) after presenting with unilateral back and lower abdominal pain with dysuria and was noted to have an acute kidney injury with a creatinine of 7.45 mg/dL and severe metabolic acidosis with a pH of 6.7 and an anion gap more than 50 mmol/L. Lactic acid was elevated at 24.2 mmol/L. Serum metformin levels were high at 14 mcg/mL (therapeutic range: 1-2 mcg/mL). She required emergent dialysis but subsequently, renal functions recovered. Risk of metformin-associated lactic acidosis (MALA) is reported to be an estimated 6.3 per 100,000 patient-years. Commonly encountered clinical scenarios such as hypoxemia, sepsis, alcohol abuse, renal injury, and shock can precipitate MALA. Early recognition allows timely initiation of appropriate therapy and reduces associated morbidity.