Antidiabetic and Renoprotective Effects of Coffea arabica Pulp Aqueous Extract through Preserving Organic Cation Transport System Mediated Oxidative Stress Pathway in Experimental Type 2 Diabetic Rats.

Coffea arabica pulp (CP) is a by-product of coffee processing. CP contains polyphenols that have exhibited beneficial effects, including antioxidant and lipid-lowering effects, as well as enhanced insulin sensitivity, in in vitro and in vivo models. How polyphenols, as found in CP aqueous extract (CPE), affect type 2 diabetes (T2D) has not been investigated. Thus, the present study examined the potential antidiabetic, antioxidant, and renoprotective effects of CPE-rich polyphenols, using an experimental model of T2D in rats induced by a high-fat diet and a single low dose of streptozotocin. The T2D rats received either 1000 mg/kg body weight (BW) of CPE, 30 mg/kg BW of metformin (Met), or a combination treatment (CPE + Met) for 3 months. Plasma parameters, kidney morphology and function, and renal organic transport were determined. Significant hyperglycemia, hypertriglyceridemia, insulin resistance, increased renal lipid content and lipid peroxidation, and morphological kidney changes related to T2D were restored by both CPE and CPE + Met treatments. Additionally, the renal uptake of organic cation, 3H-1-methyl-4-phenylpyridinium (MPP+), was reduced in T2D, while transport was restored by CPE and CPE + Met, through an up-regulation of antioxidant genes and protein kinase Cα deactivation. Thus, CPE has antidiabetic and antioxidant effects that potentially ameliorate kidney function in T2D by preserving renal organic cation transport through an oxidative stress pathway.

Spirogyra neglecta Aqueous Extract Attenuates LPS-Induced Renal Inflammation.

Spirogyra neglecta (SN), commonly named "Tao" in Thai, is a genus of filamentous green macroalgae. SN contains polyphenols such as isoquercetin, catechin, hydroquinone and kaempferol. These constituents exhibit beneficial effects including anti-oxidant, anti-gastric ulcer, anti-hyperglycaemia and anti-hyperlipidaemia in both in vitro and in vivo models. Whether SN extract (SNE) has an anti-inflammatory effect in vivo remains unclear. This study examined the effect of SNE on renal function and renal organic transport in lipopolysaccharide (LPS)-induced renal inflammation in rats. Rats were randomised and divided into normal saline (NS), NS supplemented with 1000 mg/kg body weight (BW) of SNE (NS + SNE), intraperitoneally injected with 12 mg/kg BW of LPS and LPS treated with 1000 mg/kg BW of SNE (LPS + SNE). Biochemical parameters in serum and urine, lipid peroxidation concentration, kidney function and renal organic anion and cation transports were determined. LPS-injected rats developed renal injury and inflammation by increasing urine microalbumin, total malondialdehyde (MDA) and inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß protein expression, respectively. In addition, uptake of renal organic anion, [3H]-oestrone sulphate (ES), was reduced in LPS-injected rats together with increased expression of organic anion transporter 3 (Oat3). However, the renal injury and inflammation, as well as impaired Oat3 function and protein expression, were restored in LPS + SNE rats. Accordingly, SNE could be developed as nutraceutical product to prevent inflammation-induced nephrotoxicity.

Impaired renal organic anion transport 1 (SLC22A6) and its regulation following acute myocardial infarction and reperfusion injury in rats.

Acute kidney injury (AKI) is a high frequent and common complication following acute myocardial infarction (AMI). This study examined and identified the effect of AMI-induced AKI on organic anion transporter 1 (Oat1) and Oat3 transport using clinical setting of pre-renal AKI in vivo. Cardiac ischaemia (CI) and cardiac ischaemia and reperfusion (CIR) were induced in rats by 30-min left anterior descending coronary artery occlusion and 30-min occlusion followed by 120-min reperfusion, respectively. Renal hemodynamic parameters, mitochondrial function and Oat1/Oat3 expression and function were determined along with biochemical markers. Results showed that CI markedly reduced renal blood flow and pressure by approximately 40%, while these parameters were recovered during reperfusion. CI and CIR progressively attenuated renal function and induced oxidative stress by increasing plasma BUN, creatinine and malondialdehyde levels. Correspondingly, SOD, GPx, CAT mRNAs were decreased, while TNFα, IL1ß, COX2, iNOS, NOX2, NOX4, and xanthine oxidase were increased. Mitochondrial dysfunction as indicated by increasing ROS, membrane depolarisation, swelling and caspase3 activation were shown. Early significant detection of AKI; KIM1, IL18, was found. All of which deteriorated para-aminohippurate transport by down-regulating Oat1 during sudden ischaemia. This consequent blunted the trafficking rate of Oat1/Oat3 transport via down-regulating PKCζ/Akt and up-regulating PKCα/NFκB during CI and CIR. Thus, this promising study indicates that CI and CIR abruptly impaired renal Oat1 and regulatory proteins of Oat1/Oat3, which supports dysregulation of remote sensing and signalling and inter-organ/organismal communication. Oat1, therefore, could potentially worsen AKI and might be a potential therapeutic target for early reversal of such injury.