Can daily consumption of a nephroprotective homeopathic product protect the kidneys from gentamicin toxicity?

The objective of this work was to determine whether preventive consumption of a homeopathic product via drinking water would protect mouse kidneys from a challenge with the nephrotoxic antibiotic gentamicin. We used 40 Swiss mice divided into four groups with ten animals each. The homeopathic product was supplied through water for 30 days in a preventive manner and gentamicin for 10 days to induce an experimental renal failure. The groups were as follows: Negative-CT (homeopathic and gentamicin was not provided), Positive-CT (did not receive homeopathic, but received gentamicin 40 mg/kg), T2 (received 0.002 ml of the product per animal/day, and received gentamicin 40 mg/kg), and T4 (0.004 ml of the product per animal/day and received gentamicin 40 mg/kg). On days 12 and 20, blood and tissue samples were collected from five animals in each group. No histopathological lesions were found in mouse kidneys. However, levels of thiobarbituric acid reactive substances, reactive oxygen species, and nitrite/nitrate ratios in the kidney of the Positive-CT group were higher compared to the other groups. As for glutathione S-transferase, on the 20th day, the groups that used the homeopathic product (T2 and T4) had higher activities than the positive TC. Therefore, the results suggest that prophylactic consumption of the hepatoprotective homeopathic product can decrease lipid peroxidation, nitrous stress, and oxidative stress at the renal level when consecutive doses of gentamicin induce insufficiency.

Oxidant-Induced Alterations in the Adipocyte Transcriptome: Role of the Na,K-ATPase Oxidant Amplification Loop

(1) Background: Recently we have noted that adipocyte specific expression of the peptide, NaKtide, which was developed to attenuate the Na,K-ATPase oxidant amplification loop, could ameliorate the phenotypical features of uremic cardiomyopathy. We performed this study to better characterize the cellular transcriptomes that are involved in various biological pathways associated with adipocyte function occurring with renal failure. (2) Methods: RNAseq was performed on the visceral adipose tissue of animals subjected to partial nephrectomy. Specific expression of NaKtide in adipocytes was achieved using an adiponectin promoter. To better understand the cause of gene expression changes in vivo, 3T3L1 adipocytes were exposed to indoxyl sulfate (IS) or oxidized low density lipoprotein (oxLDL), with and without pNaKtide (the cell permeant form of NaKtide). RNAseq was also performed on these samples. (3) Results: We noted a large number of adipocyte genes were altered in experimental renal failure. Adipocyte specific NaKtide expression reversed most of these abnormalities. High correlation with some cardiac specific phenotypical features was noted amongst groups of these genes. In the murine adipocytes, both IS and oxLDL induced similar pathway changes as were noted in vivo, and pNaKtide appeared to reverse these changes. Network analysis demonstrated tremendous similarities between the network revealed by gene expression analysis with IS compared with oxLDL, and the combined in vitro dataset was noted to also have considerable similarity to that seen in vivo with experimental renal failure. (4) Conclusions: This study suggests that the myriad of phenotypical features seen with experimental renal failure may be fundamentally linked to oxidant stress within adipocytes.

Influence of the Expression of Inflammatory Markers on Kidney after Fetal Programming in an Experimental Model of Renal Failure

Objective. To evaluate the expression of inflammatory markers in experimental renal failure after fetal programming. Methods. The offspring aged two and five months were divided into four groups: CC (control dams, control offspring); DC (diabetic dams, control offspring); CFA (control dams, folic acid offspring, 250 mg/Kg); and DFA (diabetic dams, folic acid offspring). Gene expression of inflammatory markers MCP-1, IL-1, NOS3, TGF-β, TNF-α, and VEGF was evaluated by RT-PCR. Results. MCP-1 was increased in the CFA and DFA groups at two and five months of age, as well as in DC5 when compared to CC5. There was a higher expression of IL-1 in the CFA2, DFA2, and DC2 groups. There was a decrease in NOS3 and an increase in TNF-α in DFA5 in relation to CFA5. The gene expression of TGF-β increased in cases that had received folic acid at two and five months, and VEGF decreased in the CFA5 and DFA5 groups. DC5 showed increased VEGF expression in comparison with CC5. Conclusions. Gestational diabetes mellitus and folic acid both change the expression of inflammatory markers, thus demonstrating that the exposure to harmful agents in adulthood has a more severe impact in cases which underwent fetal reprogramming.