Particular Matter of Motor Vehicle Exposure and High-Fat Diet Effects on Kidney Histopathology, Creatinine, and Malondialdehyde (MDA) Levels in Wistar Rats

This study aims to analyze the effect of combination of motor vehicle particular matter exposure and high-fat diet in kidney histopathology, creatinine levels, and MDA levels in Wistar rats. This study used a posttest-only control group design. Eighteen healthy male Wistar rats were divided into three groups. The intervention groups received motor vehicle fume exposure for 100 s with normal diet (X1) or high-fat diet (X2), and the control group received no exposure (C). Data analysis was processed with a SPSS 25.0 computer program by using the one-way ANOVA test followed by post hoc LSD. The degree of kidney histopathological damage showed significant differences between the X1 and X2 groups when compared with the control group (p < 0.05). The results of the creatinine level examination found a significant difference between the X2 and C groups (p < 0.05) and the treatment groups X1 and X2 (p < 0.05). The results of kidney MDA level examination showed a significant difference between the treatment groups (X1 and X2) and the control group (p < 0.05). The combination of particular matter of motor vehicle fumes exposure and high-fat diet could induce kidney damage through histopathological change and increased creatinine levels and kidney MDA levels in Wistar rats.

Protective Effect of Calcium Dobesilate Administration Against Hepatorenal Damage Induced By CCL4 In Male Mice

Purpose: Calcium dobesilate (CaD) has antioxidant and anti-inflammatory properties. In this study, the protective effects of CaD against hepatorenal damage induced by CCL4 in male mice were evaluated. Methods: Thirty male mice randomly were divided into five groups: Control, CaD 100 mg/kg, CCL4, CCL4+CaD 50 mg/kg, and CCL4+CaD 100 mg/kg. Drugs were administered orally once a day for 4-weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase and aspartate aminotransferase levels) were determined. Also, hepatic and renal tissue oxidant/antioxidant markers (glutathione peroxidase, malondialdehyde, total antioxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, and Bcl-2 protein levels were measured by immunoblotting method. The liver and kidney histopathological changes were evaluated by H&E staining.Results: CCL4 induces significant oxidative stress in the kidney and liver that was concomitant with functional and histopathological abnormalities in these organs in the CCL4 group versus the control (P<0.05). CaD could significantly improve the histopathological change in the liver and kidney tissues of CCL4+CaD 100 mg/kg mice versus the CCL4 group (P<0.05). In addition, CaD attenuated apoptosis in the liver and kidney tissues (P<0.05).Conclusion: The protective effect of CaD may be related to its anti-inflammatory and antioxidant properties.

Liver Histopathological Change and Malondialdehyde Level of Rattus Norvegicus on Administration of Curcuma Zedoaria and Paracetamol Toxic Dose

High doses of paracetamol create necrosis in the liver and produce free radicals. When liver function decreased in a long time, it will lead to severe liver damage and it will be irreversible. Rhizome of Curcuma zedoaria has the potential effect as an antioxidant, it is assumed that its properties inhibit the formation of free radicals which formed from toxic doses of paracetamol. The aim of this study was to examine the histological structure of the liver and to determine MDA levels in the administration of C. zedoaria toxic dose and paracetamol on the Rattus norvegicus. The study was used twenty-four rats divided into four groups (positive control: CMC 0.5%; negative control: paracetamol 1.35g/kg body weight; treatment group 1 (T1): C. zedoaria 105 mg/200g and paracetamol 1.35g/kg Body weight 2 hours later, and treatment group 2 (T2): paracetamol 1.35g/ kg Body weight and C. zedoaria 105 mg/200g 2 hours later). The Kruskall-Wallis test results showed MDA level did not significantly different between groups (p = 0.087). Hepatocellular changes were observed descriptively with Hematoxylin-eosin staining. Positive control showed greater hepatocellular changes rather than other groups, hepatocyte cells were enlarged with cytoplasm showing eosinophilic granules infiltrates, enlarged irregular nuclei, nucleolus prominent, there are many necrosis cells.

Synthesis, Characterization and Safety Evaluation of Sericin-Based Hydrogels for Controlled Delivery of Acyclovir

Conventional formulations of antiviral drug acyclovir have various limitations such as low bioavailability. The current study was aimed at developing polymeric matrices for the controlled delivery of acyclovir using sericin as polymer and acrylic acid (AA) as a monomer. The free radical polymerization technique was used for hydrogel formulation. Briefly, sericin was chemically cross-linked with acrylic acid. N′-N′-methylene bis-acrylamide (MBA) and ammonium persulfate (APS) were used as cross-linker and initiator, respectively. FTIR spectra showed that acyclovir was successfully loaded into sericin hydrogel. SEM micrographs revealed that the outer surface was solid-like and smooth. According to DSC thermograms, the developed polymeric network was thermally stable. Amorphous nature of acyclovir was observed in XRD. The pH of medium and reactants’ concentration affected swelling dynamics and acyclovir release pattern. In addition, drug release occurred through a diffusion-controlled process. Sericin hydrogel suspension was well tolerable up to 3800 mg/kg of rabbits’ body weight. Haematology and serum chemistry results were well within the range signifying normal liver and kidney functions. Similarly, histopathology slides of the rabbit’s vital organs were also in normal condition without causing any histopathological change. It was concluded from the findings that sericin-co-AA polymeric matrices are ideal for the pH-dependent delivery of acyclovir.

Genetic Characteristics of Avian Influenza Virus Isolated from Wild Birds in South Korea, 2019–2020

Wild aquatic birds, a natural reservoir of avian influenza viruses (AIVs), transmit AIVs to poultry farms, causing huge economic losses. Therefore, the prevalence and genetic characteristics of AIVs isolated from wild birds in South Korea from October 2019 to March 2020 were investigated and analyzed. Fresh avian fecal samples (3256) were collected by active monitoring of 11 wild bird habitats. Twenty-eight AIVs were isolated. Seven HA and eight NA subtypes were identified. All AIV hosts were Anseriformes species. The HA cleavage site of 20 representative AIVs was encoded by non-multi-basic amino acid sequences. Phylogenetic analysis of the eight segment genes of the AIVs showed that most genes clustered within the Eurasian lineage. However, the HA gene of H10 viruses and NS gene of four viruses clustered within the American lineage, indicating intercontinental reassortment of AIVs. Representative viruses likely to infect mammals were selected and evaluated for pathogenicity in mice. JB21-58 (H5N3), JB42-93 (H9N2), and JB32-81 (H11N2) were isolated from the lungs, but JB31-69 (H11N9) was not isolated from the lungs until the end of the experiment at 14 dpi. None of infected mice showed clinical sign and histopathological change in the lung. In addition, viral antigens were not detected in lungs of all mice at 14 dpi. These data suggest that LPAIVs derived from wild birds are unlikely to be transmitted to mammals. However, because LPAIVs can reportedly infect mammals, including humans, continuous surveillance and monitoring of AIVs are necessary, despite their low pathogenicity.

The therapeutic effects of FGF21 on diabetic nephropathy are realized by augmenting autophagy via AMPK/mTOR signaling pathway

Accumulating evidence demonstrates that FGF21 plays a preventive role in the development of diabetic nephropathy (DN). However, little is known about the therapeutical effects of FGF21 on DN and underlying mechanism. In this study, FGF21 significantly ameliorated blood glucose, HbAlc, insulin resistance, renal function and histopathological change in DN mice (BKS-Leprem2Cd479/Gpt), which develop abnormalities in renal morphology and function. Our results showed that administration of FGF21 upregulated the autophagy related genes LC3Ⅱ and BCL-1 mRNA and protein expression levels. D-glucose was used for high glucose (HG) model in mesangial cells. The results showed that treatment with FGF21 reduced the levels of ROS, AGEs and inflammatory cytokines and significantly downregulated the protein expression of PCNA. Meanwhile, FGF21 significantly enhanced the expression of LC3Ⅱ and BCL-1. Besides, Our studies showed that administration of FGF21 significantly upregulated the phosphorylation of AMPK and downregulated phosphorylation of mTOR. Meanwhile, the effects of FGF21 on autophagy were reversed by siRNA against β-klotho. In conclusion, The therapeutic effects of FGF21 on diabetic nephropathy are realized and FGF21 ameliorates mesangial cell glucotoxicity and abnormal proliferation in vitro by augmenting autophagy via AMPK/mTOR pathway. These results suggest that FGF21 can be a therapeutic target against DN.

Mesenchymal Stem Cells Ameliorate Interstitial Fibrosis in Adenine-induced Nephropathy Based on Renal Proteomics

Background: Tubulointerstitial fibrosis (TIF) is one of the main pathological features of various progressive renal damages and chronic kidney diseases. Mesenchymal stromal cells (MSCs) have been verified with significant improvement in the therapy of fibrosis diseases, but the mechanism is still unclear. We attempted to explore the new mechanism and therapeutic target of MSCs against renal fibrosis based on renal proteomics.Methods: TIF model was induced by adenine gavage. Bone marrow derived MSCs was injected by tail vein after modeling. Fibrosis biomarkers or extracellular matrix proteins and histopathological change were assessed by Masson staining, Sirius red staining, immunohistochemistry, and western blot. Renal proteomics was analyzed using iTRAQ-based mass spectrometry.Results: MSCs treatment clearly decreased the expression of α-SMA, collagen type I, II, III, TGF-β1, p-Smad2/3, IL-6, IL-1β, and TNFα compared with model rats, while p38 MAPK increased. 6,213 proteins were identified, but only 40 proteins exhibited significant differences (30 upregulated, 10 downregulated) compared MSCs group with the model group. Bioinformatics analysis revealed that these proteins play important roles in the proliferation, inflammatory and immune responses, apoptosis, phagosome, etc. According to literatures and bioinformatics analysis, the most markedly downregulated protein, galectin3, was further assessed by quantitative PCR and western blot in renal tissues. Galectin3 levels were downregulated in adenine-induced renal tissues and TGF-β1 induced tubular epithelial cells and interstitial fibroblasts in consistent with iTRAQ after MSCs treatment.Conclusion: The founds suggest that galectin3 maybe involves in the antifibrotic mechanisms of MSCs therapy for tubulointerstitial fibrosis as well as a possible therapeutic target.

Eudragit L-100 Capsules Aromatize and Quaternerize Chitosan for Insulin Nanoparticle Oral Delivery During Toxic Oxidative Stress in Rat Liver and Kidney

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.

HEPATOPROTECTIVE ACTIVITY OF MERREMIA BORNEENSIS AGAINST CARBON TETRACHLORIDE (CCl4)-INDUCED ACUTE LIVER DAMAGE IN RATS: A BIOCHEMICAL AND HISTOPATHOLOGICAL EVALUATION

Objective: The pathogenesis of various liver injuries involves oxidative damage. This research was planned to examine the effects of Mereemia borneensis extract on hepatic oxidative damage caused by carbon tetrachloride (CCl4) in rats. Methods: Sprague Dawley rats were exposed to M. borneensis (125 and 250 mg/kg b. wt.) once daily for 14 d followed by two doses of CCl4 (1.2 ml/kg b. wt.). After 2 w, the rats were sacrificed and hepatoprotective analysis was done. Results: Orally administration of CCl4 enhances serum transaminase (ALT; alanine transaminase and AST; aspartate transaminase), γ-glutamyl transpeptidase, lipid peroxidation, reduction in glutathione, catalase, glutathione reductase, glutathione peroxidase, quinone reductase and glutathione S-transferase. Pretreatment of rats with M. borneensis at 125 and 250 mg/kg body weight significantly reduced levels of ALT, AST, γ-glutamyl transpeptidase and lipid peroxidation of CCl4 treated rats. Pretreatment with M. borneensis against rats treated with CCl4, hepatic enzymatic and non-enzymatic antioxidant molecules have increased significantly. A decreased histopathological change in the liver is further evidence of the protective effect of M. borneensis. Conclusion: Our data suggest that M. borneensis can be a potential hepatoprotective agent in preventing or treating degenerative diseases that involve oxidative stress.