Dipeptidyl peptidase type 4 (DPP-4) inhibitors were reported to have beneficial effects in experimental models of chronic kidney disease. The underlying mechanisms are not completely understood. However, these effects could be mediated via the glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP1R) pathway. Here we investigated the renal effects of the DPP-4 inhibitor linagliptin in Glp1r-/- knock out and wild-type mice with 5/6 nephrectomy (5/6Nx). Mice were allocated to groups: sham+wild type+placebo; 5/6Nx+ wild type+placebo; 5/6Nx+wild type+linagliptin; sham+knock out+placebo; 5/6Nx+knock out+ placebo; 5/6Nx+knock out+linagliptin. 5/6Nx caused the development of renal interstitial fibrosis, significantly increased plasma cystatin C and creatinine levels and suppressed renal gelatinase/collagenase, matrix metalloproteinase-1 and -13 activities; effects counteracted by linagliptin treatment in wildtype and Glp1r-/- mice. Two hundred ninety-eight proteomics signals were differentially regulated in kidneys among the groups, with 150 signals specific to linagliptin treatment as shown by mass spectrometry. Treatment significantly upregulated three peptides derived from collagen alpha-1(I), thymosin β4 and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) and significantly downregulated one peptide derived from Y box binding protein-1 (YB-1). The proteomics results were further confirmed using western blot and immunofluorescence microscopy. Also, 5/6Nx led to significant up-regulation of renal transforming growth factor-β1 and pSMAD3 expression in wild type mice and linagliptin significantly counteracted this up-regulation in wild type and Glp1r-/- mice. Thus, the renoprotective effects of linagliptin cannot solely be attributed to the GLP-1/GLP1R pathway, highlighting the importance of other signaling pathways (collagen I homeostasis, HNRNPA1, YB-1, thymosin β4 and TGF-β1) influenced by DPP-4 inhibition.

Background: The potent antioxidant lycopene has attracted a large amount of research attention given its potential health benefits. We aimed to assess the antimicrobial, anti-inflammatory, and antioxidant properties of lycopene (Lyc), selenium nanoparticles (Se-NPs), and lycopene selenium nanoparticles (Lyc-Se-NPs). Methods: FTIR, polydispersity index, and zeta potential evaluations provided a complete characterization of the synthesized Lyc-Se-NPs. The broth dilution method and a crystal violet microtiter plate assay were employed to assess the antibacterial and antibiofilm activity, respectively. The rat wound infection model was performed to study the anti-inflammatory effect. Findings: The Lyc-Se-NPs had a zeta potential range of −16.93 to −31.04 mV and a mean particle size of 126.6 ± 3.12 nm. All peaks’ percentage transmittance decreased, according to the FTIR analysis of the Lyc-Se-NPs, with the exception of one peak at 2924.22 cm⁻¹, which is suggestive of C-H stretching. The mean scavenging concentrations for Lyc-Se-NPs in the DPPH and ABTS radical scavenging experiments were 3.85 ± 0.65 and 4.26 ± 0.7 µg/mL, respectively. For S. aureus, the Lyc-Se-NPs’ MIC values varied from 64 to 1024 µg/mL. CLSM verified that S. aureus treated with sub-MICs of Lyc-Se-NPs showed a significant reduction in biofilm formation. Furthermore, the group treated with 50 mg of Lyc-Se-NPs showed the quickest rate of wound healing. They demonstrated a notable elevation of the HO⁻¹ content in skin tissues, together with the greatest downregulation of TNF-α, IL-1β, and COX-2. Conclusions: The distinguishing features of Lyc-Se-NPs reveal that this unique compound is a promising antibacterial, antioxidant, and anti-inflammatory agent.

Hesperidin (Hes) functions as a strong antioxidant and anti-inflammatory to guard against damage to the heart, liver, and kidneys. Nevertheless, due to its restricted solubility and bioavailability, a delivery method is required for it to reach a specific organ. In this study, ion gelation was used to synthesize a chitosan/hesperidin nanoformulation. Numerous characterization techniques, such as zeta potential, particle size, XRD, TEM, SEM, and FTIR analyses, were used to corroborate the synthesis of hesperidin nanoparticles (Hes-NPs). Male albino mice were given a pretreatment dose of 100 mg/kg, PO, of Hes or Hes-NPs, which was administered daily for 14 days before the induction of doxorubicin nephrotoxicity on the 12th day. Kidney function (urea and creatinine levels) was measured. Lipid peroxidation (MDA) and antioxidant enzyme (CAT and SOD) activities were estimated. TNF-α, IL-1β, and VEGF content; histopathological examination of kidney tissue; and immunohistochemical staining of NF-κB, Caspase-3, BAX, Bcl-2, and TGF-β1 were evaluated. The gene expressions of Sirt-1, Bcl-2, VEGF, HIF1-α, and Kim-1 were also considered. The results showed that pretreatment with Hes or Hes-NPs reduced doxorubicin’s nephrotoxic effects, with Hes-NPs showing the greatest reduction. Kidney enzyme and MDA content were lowered in response to the Hes or Hes-NP pretreatment, whereas antioxidant enzyme activities were increased. Hes or Hes-NP pretreatment suppressed the levels of TNF-α, IL-1β, VEGF, NF-κB, Caspase-3, BAX, and TGF-β1; however, pretreatment increased Bcl-2 protein levels. Furthermore, the gene expressions of Sirt-1, Bcl-2, VEGF, HIF1-α, and Kim-1 were considerably higher with Hes-NP than with Hes treatment. These results suggest that Hes-NP treatment might reduce DOX-induced nephrotoxicity in mice via modulating Sirt-1/HIF1-α/VEGF/NF-κB signaling to provide antioxidant, anti-inflammatory, and anti-apoptotic effects.