Hypolipidemic and Antioxidant Effects of Guishe Extract from Agave lechuguilla, a Mexican Plant with Biotechnological Potential, on Streptozotocin-Induced Diabetic Male Rats

In the present study, we used a by-product from Agave lechuguilla (guishe) to test its antidiabetic effect, hypolipidemic activity, and capacity to mitigate the oxidative stress in kidney mitochondria from streptozotocin-induced diabetic rats. Orally, a crude aqueous extract from lyophilized guishe was administered over 5 weeks at different doses. Blood glucose and body weight were monitored. Also, blood chemistry, bilirubin, and alanine aminotransferase were assayed. Furthermore, the activity of catalase, thiobarbituric acid reactive species, mitochondrial superoxide dismutase, glutathione and glutathione peroxidase were determined in isolated kidney mitochondria. Our results show that guishe extracts have no antidiabetic properties at any dose. Nevertheless, it was able to diminish serum triglyceride levels and regulate the oxidative stress observed in isolated kidney mitochondria. These observations indicate that the aqueous extract from guishe can be used to treat abnormalities in serum lipids, as a hypolipidemic, and mitigate the oxidative stress, as an antioxidant, occurring during diabetes.

The effect of exogenous peroxiredoxin 6 on morphofunctional state of isolated rat kidney

Objective: to investigate the role of peroxiredoxin 6 (PRX6) in preserving the morphofunctional state of ischemic isolated kidney during perfusion.Materials and methods. The model of an isolated perfused rat kidney was used. Ischemia time was 5 and 20 minutes, perfusion was 50 minutes. To evaluate the effectiveness of PRX6 at different ischemia times, we used the conventional criteria of kidney function and histological methods.Results. During short warm ischemia times, exogenous PRX6 improves the morphofunctional state of an isolated kidney during perfusion. During this period, the main criteria for functioning of the isolated ischemic kidney reach acceptable values, renal parenchyma is without severe damage. By the end of perfusion, there was an increase in urine flow rate, glomerular filtration rate, fractional glucose reabsorption, urine urea concentration and proportion of primary urine from 1.5 to 2 times compared with the control lesion. At 20-minute ischemia, the isolated kidney can be recognized as non-viable according to the functioning criteria; the positive effect of PRX6 is leveled.Conclusion. The use of recombinant peroxiredoxin 6 for preserving the morphofunctional state of isolated kidneys can be an effective approach in preventing ischemia–reperfusion injury.

Nephrotoxic Potential of Putative 3,5-Dichloroaniline (3,5-DCA) Metabolites and Biotransformation of 3,5-DCA in Isolated Kidney Cells from Fischer 344 Rats

The current study was designed to explore the in vitro nephrotoxic potential of four 3,5-dichloroaniline (3,5-DCA) metabolites (3,5-dichloroacetanilide, 3,5-DCAA; 3,5-dichlorophenylhydroxylamine, 3,5-DCPHA; 2-amino-4,6-dichlorophenol, 2-A-4,6-DCP; 3,5-dichloronitrobenzene, 3,5-DCNB) and to determine the renal metabolism of 3,5-DCA in vitro. In cytotoxicity testing, isolated kidney cells (IKC) from male Fischer 344 rats (~4 million/mL, 3 mL) were exposed to a metabolite (0–1.5 mM; up to 90 min) or vehicle. Of these metabolites, 3,5-DCPHA was the most potent nephrotoxicant, with 3,5-DCNB intermediate in nephrotoxic potential. 2-A-4,6-DCP and 3,5-DCAA were not cytotoxic. In separate experiments, 3,5-DCNB cytotoxicity was reduced by pretreating IKC with antioxidants and cytochrome P450, flavin monooxygenase and peroxidase inhibitors, while 3,5-DCPHA cytotoxicity was attenuated by two nucleophilic antioxidants (glutathione and N-acetyl-L-cysteine). Incubation of IKC with 3,5-DCA (0.5–1.0 mM, 90 min) produced only 3,5-DCAA and 3,5-DCNB as detectable metabolites. These data suggest that 3,5-DCNB and 3,5-DCPHA are potential nephrotoxic metabolites and may contribute to 3,5-DCA induced nephrotoxicity in vivo. In addition, the kidney can bioactivate 3,5-DCNB to toxic metabolites, and 3,5-DCPHA appears to generate reactive metabolites to contribute to 3,5-DCA nephrotoxicity. In vitro, N-oxidation of 3,5-DCA appears to be the primary mechanism of bioactivation of 3,5-DCA to nephrotoxic metabolites.

Isolated kidney injury: international recommendations and Moscow standards

Introduction. Currently, existing classifications of kidney injury severity do not indicate the choice of a particular treatment method. The purpose of our study was to retrospectively evaluate the management of patients with isolated kidney injury. Materials and methods. A retrospective analysis of the results of treatment of 52 patients with isolated kidney injury was performed. All patients according to the AAST (American Association for Surgery and Trauma) classification were divided into five groups: group I – 25 (48%) people, group II – 7 (13%), group III – 6 (12%), group IV – 11 (21%), group V – 3 (6%). Results. In patients with I degree of damage (n=25), no invasive methods of diagnosis and treatment were required: 12 (48%) patients were discharged from the hospital after active observation, 13 (52%) patients underwent complex conservative treatment. In group II (n=7), in most cases (n=6; 86%), treatment was also conservative, with the exception of one patient who underwent diagnostic angiography. All patients with grade III damage (n=6) underwent diagnostic angiography, and in 2 (33%) cases, selective embolization of the renal artery branch was performed. In group IV (n=11), diagnostic angiography was performed in 9 (82%) patients, however, selective embolization of the renal artery branch was effective in 7 (78%) patients, and the remaining 2 patients underwent organ-preserving surgery. Only 2 (18%) patients with grade IV damage had a nephrectomy. None of the patients with V degree of damage (n=3) could avoid nephrectomy. Discussion. Based on our own data and the results of foreign studies, it was concluded that the stability of hemodynamics is a fundamental sign of determining the tactics of treating a patient. In patients with stable hemodynamics with kidney injury, selective embolization of the branches of the renal artery is indicated. Angiography and embolization can be performed for kidney injuries of any degree, but it is most justified for complex injuries. The effectiveness of embolization is obvious, but unsuccessful embolization is a direct indication for renal revision. It should also be noted that open kidney injury is an absolute indication for revision. Conclusions. X-ray endovascular technologies are widely used in patients with isolated kidney injury, which in turn dictates the need to include this type of care in the standards of treatment of patients in this group.

Kidney and Lung ACE2 expression after an ACE inhibitor or an Ang II receptor blocker: implications for COVID-19

ABSTRACTBackgroundThere have been concerns that ACE inhibitors and Ang II receptor blockers may cause an increase in ACE2, the main receptor for SARs-CoV-2.MethodsKidneys from two genetic models of kidney ACE ablation and mice treated with captopril or telmisartan were used to examine ACE2 in isolated kidney and lung membranes.ResultsIn a global ACE KO mice, ACE2 protein abundance in kidney membranes was reduced to 42 % of wild type, p < 0.05. In ACE 8/8 mice that over-expresses cardiac ACE protein but also has no kidney ACE expression, ACE2 protein in kidney membranes was also decreased (38 % of the WT, p<0.01). In kidney membranes from mice that received captopril or telmisartan for 2 weeks there was a reduction in ACE2 protein (37% in captopril treated p<0.01) and 76% in telmisartan treated p <0.05). In lung membranes the expression of ACE2 was very low and not detected by western blotting but no significant differences in terms of ACE2 activity could be detected in mice treated with captopril (118% of control) or telmisartan (93% of control).ConclusionsGenetic kidney ACE protein deficiency, suppressed enzymatic activity by Captopril or blockade of the AT1 receptor with telmisartan are all associated with a decrease in ACE2 in kidney membranes. ACE2 protein in kidney or lungs is decreased or unaffected by RAS blockers indicating that these medications can not pose a risk for SARS-CoV-2 infection related to amplification of ACE2 at these two target sites for viral entry.

Clinical Characteristics of 162 Patients with Drug-Induced Liver and/or Kidney Injury

Context. Drug-induced liver and kidney injuries are the most common adverse drug reactions in the clinic, and they have similar pathogeneses. Aims. To analyze the clinical characteristics of patients with drug-induced liver and/or kidney injury. Settings and Design. This was a retrospective study. Methods and Materials. We analyzed data from 162 patients with drug-induced liver and/or kidney injury from 2008 to 2018 at the Chinese Rocket Force Characteristic Medical Center. Univariate and multivariate logistic analyses were performed on the drugs used, sex, age, weight, complications, and laboratory test results. Statistical analysis was performed using SPSS 25.0 statistical software. Results. (1) The most common drugs causing organ injury in this study were antineoplastic drugs, antibiotics, traditional Chinese medicine, lipid-lowering drugs, and nonsteroidal anti-inflammatory drugs. (2) Among 22 patients with drug-induced liver and kidney injuries, 68.18% had a hepatocellular pattern, 13.64% had a mixed pattern, and 18.18% had a cholestatic pattern. Among the three groups, the P value for creatinine was 0.002. (3) The P value for urinary protein between the isolated kidney injury group and the liver and kidney injury group was 0.028. (4) Multivariate analysis showed that, among the drug-induced renal injury patients and all injury patients, those with a higher neutrophil percentage had a lower risk of liver injury (OR = 0.574, 95% CI: 0.390–0.846; OR = 0.545, 95% CI: 0.396–0.749). Conclusions. (1) The serum creatinine level was higher in liver injury patients with the cholestatic pattern than in those with the hepatocellular or mixed pattern. (2) There was a significant difference in urinary protein between the isolated kidney and the liver and kidney injury groups. (3) Among patients with drug-induced organ injury, those with a higher neutrophils percentage had a lower risk of liver injury.