Plasma and milk metabolomics revealed changes in amino acid metabolism in Holstein dairy cows under heat stress.

Our understanding of metabolic alterations triggered by heat stress is incomplete, which limits the designing of nutritional strategies to mitigate negative productive and health effects. Thus, this study aimed to explore the metabolic responses of heat-stressed dairy cows to dietary supplementation with vitamin D3/Ca and vitamin E/Se. Twelve multiparous Holstein cows were enrolled in a split-plot Latin square design with two distinct vitamin E/Se supplementation levels, either at a low (ESe-, n = 6, 11.1 IU/kg vitamin E and 0.55 mg/kg Se) or a high dose (ESe+, n = 6 223 IU/kg vitamin E and 1.8 mg/kg Se) as the main plot. Treatment subplots, arranged in a replicated 3 × 3 Latin square design, comprised heat challenge (Temperature Humidity Index, THI: 72.0-82.0) supplemented with different levels of vitamin D3/Ca: either low (HS/DCa-, 1 012 IU/kg and 0.73%, respectively) or high (HS/DCa+, 3 764 IU/kg and 0.97%, respectively), and a pair-fed control group in thermoneutrality (THI = 61.0-64.0) receiving the low dose of vitamin D3/Ca (TN). The liquid chromatography-mass spectrometry-based metabolome profile was determined in blood plasma and milk sampled at the beginning (day 0) and end (day 14) of each experimental period. The results were analyzed for the effect of (1) TN vs. HS/ESe-/DCa-, and (2) the vitamin E/Se and vitamin D3/Ca supplementation. No group or group × day effects were detected in the plasma metabolome (false discovery rate, FDR > 0.05), except for triglyceride 52:2 being higher (FDR = 0.03) on day 0 than 14. Taurine, creatinine and butyryl-carnitine showed group × day interactions in the milk metabolome (FDR ≤ 0.05) as creatinine (+22%) and butyryl-carnitine (+190%) were increased (P < 0.01) on day 14, and taurine was decreased (-65%, P < 0.01) on day 14 in the heat stress (HS) cows, compared with day 0. Most compounds were unaffected by vitamin E/Se or vitamin D3/Ca supplementation level or their interaction (FDR > 0.05) in plasma and milk, except for milk alanine which was lower (-69%, FDR = 0.03) in the E/Se+ groups, compared with E/Se-. Our results indicated that HS triggered more prominent changes in the milk than in the plasma metabolome, with consistent results in milk suggesting increased muscle catabolism, as reflected by increased creatinine, alanine and citrulline levels. Supplementing with high levels of vitamin E/Se or vitamin D3/Ca or their combination did not appear to affect the metabolic remodeling triggered by HS.

Dietary Potassium Supplementation Reduces Chronic Kidney Lesions Independent of Blood Pressure in Deoxycorticosterone-Acetate and High Sodium Chloride-Treated Mice.

We have previously shown that an excess of deoxycorticosterone acetate and high sodium chloride intake (DOCA/salt) in one-renin gene mice induces a high urinary Na/K ratio, hypokalemia, and cardiac and renal hypertrophy in the absence of hypertension. Dietary potassium supplementation prevents DOCA/salt-induced pathological processes. In the present study, we further study whether DOCA/salt-treated mice progressively develop chronic inflammation and fibrosis in the kidney and whether dietary potassium supplementation can reduce the DOCA/salt-induced renal pathological process. Results showed that (1) long-term DOCA/salt-treated one-renin gene mice developed severe kidney injuries including tubular/vascular hypertrophy, mesangial/interstitial/perivascular fibrosis, inflammation (lymphocyte's immigration), proteinuria, and high serum creatinine in the absence of hypertension; (2) there were over-expressed mRNAs of plasminogen activator inhibitor-1 (PAI-1), fibronectin, collagen type I and III, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP1), transforming growth factor-ß (TGF-ß), tumor necrosis factor-alpha (TNF-α), osteopontin, Nuclear factor kappa B (NF-κB)/P65, and intercellular adhesion molecule (ICAM)-1; and (3) dietary potassium supplementation normalized urinary Na/K ratio, hypokalemia, proteinuria, and serum creatinine, reduced renal hypertrophy, inflammations, and fibrosis, and down-regulated mRNA expression of fibronectin, Col-I and III, TGF-ß, TNF-α, osteopontin, and ICAM without changes in the blood pressure. The results provide new evidence that potassium and sodium may modulate proinflammatory and fibrotic genes, leading to chronic renal lesions independent of blood pressure.

Possible role of pomegranate fruit in reversing renal damage in rats exposed to Phenylhydrazine.

Background: Pomegranate granatum (molasses and peels) and its constituents showed protective effects against natural toxins such as phenylhydrazine (PHZ) as well as chemical toxicants such as arsenic, diazinon, and carbon tetrachloride. Aim: The current study aimed to assess the effect of pomegranate molasses (PM), white peel extract, and red peel extract on nephrotoxicity induced by PHZ. Methods: 80 male rats were divided into eight equal groups; a control group, PM pure group, white peel pomegranate pure group, red peel pomegranate pure group, PHZ group, PM + PHZ group, white peel pomegranate + PHZ group and red peel pomegranate + PHZ group. Kidney function, inflammation markers, antioxidant activities, and renal tissue histopathology were investigated. Results: The results revealed that PHZ group showed a significant increase in lactate Dehydrogenase (LDH), malondialdehyde (MDA), creatinine, uric acid, BUNBUN, C - reactive protein (CRP), tumor necrosis factor, thiobarbituric acid reactive substances (TBARSs), and total antioxidant capacity (TAC) with a significant decrease of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) as compared with a control group. Other pomegranate-treated and PHZ co-treated groups with pomegranate showed a significant decrease of LDH, MDA, creatinine, uric acid, BUN, tumor necrosis factor, TBARSs, and TAC with a significant increase of CAT, GPx, and SOD as compared with PHZ group. Conclusion: Collectively, our data suggest that red, white peels, and molasses have anti-toxic and anti-inflammatory effects on renal function and tissues.

The Protective Potential of Petroselinum crispum (Mill.) Fuss. on Paracetamol-Induced Hepatio-Renal Toxicity and Antiproteinuric Effect: A Biochemical, Hematological, and Histopathological Study.

Background and Objectives: Paracetamol overdose is a significant global issue due to its widespread use, which can lead to a lack of awareness regarding its potential side effects. Paracetamol can harm the liver, possibly resulting in liver failure. Conversely, this study employed extracts from Petroselinum crispum (PC), known for its rich content of bioactive compounds, with demonstrated antioxidant properties shown in previous research as well as protective effects against various diseases. The primary objective of this study was to investigate the potential protective effects of Petroselinum crispum on altered hematological and biochemical parameters in the blood of rats exposed to paracetamol. Materials and Methods: The study involved twenty Wistar rats divided into four groups. Different groups of male rats were administered PC extract at 200 mg/kg body weight daily for 15 days, along with a standard reference dose of paracetamol at 200 mg/kg. The study assessed hepatoprotection capacity by analyzing liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, albumin, and lipid profiles. Renal safety was evaluated through creatinine, urea, uric acid, lactate dehydrogenase (LDH), and total protein. Additionally, histopathological examinations of the liver and kidneys were conducted. Results: Following Paracetamol overdose, there were reductions in hemoglobin levels, serum total protein, albumin, and uric acid. Paracetamol overdose also elevated levels of several blood biomarkers, including creatinine, urea, nitrogen, ALT, AST, triglycerides, LDH activity, white blood cell count, and platelet count compared to the control group. However, using an ethanolic extract of Petroselinum crispum significantly mitigated the severity of these alterations and the extent of the effect correlated with the dose administered. Parsley extract helped prevent proteinuria and low hemoglobin, which are common side effects of Paracetamol. Conclusions: Therefore, parsley may hold promise in managing liver and kidney conditions-particularly in addressing proteinuria. Ultimately, these results may have implications for human health by potentially mitigating paracetamol-induced renal, hepatic, and hematological toxicity.

Qizhi Jiangtang capsule activates podocyte autophagy in diabetic kidney disease by inhibiting phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways.

OBJECTIVE: To investigate the therapeutic action and mechanism of the Qizhi Jiangtang capsule (, QZJT) on diabetic kidney disease (DKD) treatment. METHODS: This experiment used db/db mice and podocytes (MPC5) to develop DKD model. Evaluation of the effect of the QZJT on db/db mice by testing urine and blood biochemical parameters (24-h urinary albumin, serum creatinine, blood urine nitrogen), pathological kidney injury, and podocyte integrity. Moreover, autophagosomes in podocytes of DKD mice and cultured podocytes were detected using electron microscopy. Additionally, Western blotting was applied to detect the expression of podocyte marker protein (podocin), autophagy-associated proteins, and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway changes and . RESULTS: QZJT significantly reduced urine protein, blood nitrogen urea, and serum creatinine and showed histological restoration of renal tissues. QZJT also significantly improved the down-regulation of podocin and foot fusion and effacement in db/db mice. QZJT increased autophagic vesicles in mice and cultured podocytes. QZJT also upregulated microtubule-associated protein 1 light chain 3-II (LC3-II) / (LC3-I) and Beclin-1 and downregulated phosphorylated-PI3K (p-PI3K), p-AKT, and p-mTOR in db/db mice and MPC5 cells. However, autophagy inhibitor 3-methyladenine partially alleviated the above effects in MPC5 cells. CONCLUSIONS: These results showed that the QZJT can enhance podocyte autophagy and ameliorate podocyte injury in DKD by inhibiting the PI3K/AKT/mTOR signaling pathway.

Effects of Mexican Ganoderma lucidum extracts on liver, kidney, and the gut microbiota of Wistar rats: A repeated dose oral toxicity study.

Well-characterized and standardized extracts of a Mexican genotype of Ganoderma lucidum (Gl), a medicinal mushroom, cultivated on oak sawdust (Gl-1) or oak sawdust plus acetylsalicylic acid (Gl-2, ASA), have been shown to exert antioxidant, hypocholesterolemic, anti-inflammatory, prebiotic, and anticancer properties. However, toxicity analyses still need to be carried out. Different doses of these Gl-1 or Gl-2 extracts were administered to Wistar rats for 14 days in a repeated dose oral toxicity study. We assessed the external clinical signs, biochemical parameters, liver and kidney tissues, injury and inflammation biomarkers, gene expression, inflammatory responses, proinflammatory mediators, and gut microbiota. Gl extracts had no significant adverse, toxic or harmful effects on male and female rats compared to the control groups. No injury or dysfunction were recorded in the kidney or liver, as there were no significant abnormal variations in organ weight, tissue histopathology, serum biochemical parameters (C-reactive protein, creatinine, urea, glucose, ALT and AST transaminases, TC, LDL-c, TG, HDL-c), urinary parameters (creatinine, urea nitrogen, albumin, the albumin-to-creatinine ratio, glucose), injury and inflammatory biomarkers (KIM-1/TIM-1, TLR4, and NF-кB protein expression; IL-1ß, TNF-α and IL-6 gene expression), or the expression of genes linked to cholesterol metabolism (HMG-CoA, Srebp2, Ldlr). Gl-1 and Gl-2 extracts showed prebiotic effects on the gut microbiota of male and female Wistar rats. Bacterial diversity and relative bacterial abundance (BRA) increased, positively modulating the Firmicutes/Bacteroidetes ratio. The ASA (10 mM) added to the substrate used for mushroom cultivation changed properties and effects of the Gl-2 extract on Wistar rats. The no-observed-adverse-effect-level (NOAEL) was 1000 mg/kg body weight/day of Gl-1 or Gl-2 extracts. Clinical trials are recommended for further exploring the potential therapeutic applications of studied extracts.

Nephroprotective effects of honokiol in a high-fat diet-streptozotocin rat model of diabetic nephropathy.

AIMS: Diabetic nephropathy (DN) is the foremost basis of end-stage kidney failure implicating endoplasmic reticulum (ER) stress and dysregulation of Rho kinase/Rock pathway. Magnolia plants are used in traditional medicine systems in Southeast Asia owing to bioactive phytoconstituents. Earlier, honokiol (Hon) exhibited therapeutic potential in experimental models of metabolic, renal, and brain disorders. In the present study, we evaluated potential of Hon against DN and possible molecular mechanisms. MAIN METHODS: In the existing experiments, high-fat diet (HFD) (17 weeks) and streptozotocin (STZ) (40 mg/kg once) induced DN rats were orally treated with Hon (25, 50, 100 mg/kg) or metformin (150 mg/kg) for 8 weeks. KEY FINDINGS: Hon attenuated albuminuria, blood biomarkers (e.g., urea nitrogen, glucose, C-reactive protein, and creatinine) and ameliorated lipid profile, electrolytes levels (Na+/K+), and creatinine clearance against DN. Hon significantly decreased renal oxidative stress and inflammatory biomarkers against DN. Histomorphometry and microscopic analysis revealed nephroprotective effects of Hon marked by a decrease in leukocyte infiltration, renal tissue damage, and urine sediments. RT-qPCR showed that Hon treatment attenuated mRNA expression of transforming growth factor-ß1 (TGF-ß1), endothelin-1 (ET-1), ER stress markers (GRP78, CHOP, ATF4, and TRB3), and Rock 1/2 in DN rats. Data from ELISA supported a decrease in levels of TGF-ß1, ET-1, ER stress markers, and Rock1/2 by Hon. SIGNIFICANCE: Hon attenuated hyperglycemia, redox imbalance, and inflammation and improved renal functions in rats. Hon alleviates DN pathogenesis possibly by attenuating ER stress and Rock pathway.

Tetrahydrocurcumin Add-On therapy to losartan in a rat model of diabetic nephropathy decreases blood pressure and markers of kidney injury.

Tetrahydrocurcumin (THC), a principal metabolite of curcumin, was tested in a rat model of type 2 diabetes mellitus. THC was administered via daily oral gavage with the lipid carrier polyenylphosphatidylcholine (PPC) as add-on therapy to losartan (angiotensin receptor blocker) to examine effects on kidney oxidative stress and fibrosis. A combination of unilateral nephrectomy, high-fat diet and low-dose streptozotocin was used to induce diabetic nephropathy in male Sprague-Dawley rats. Animals with fasting blood glucose >200 mg/dL were randomized to PPC, losartan, THC + PPC or THC + PPC + losartan. Untreated chronic kidney disease (CKD) animals had proteinuria, decreased creatinine clearance, and evidence of kidney fibrosis on histology. THC + PPC + losartan treatment significantly lowered blood pressure concurrent with increased messenger RNA levels of antioxidant copper-zinc-superoxide dismutase and decreased protein kinase C-α, kidney injury molecule-1 and type I collagen in the kidneys; there was decreased albuminuria and a trend for increased creatinine clearance compared to untreated CKD rats. There was decreased fibrosis on kidney histology in PPC-only and THC-treated CKD rats. Plasma levels of kidney injury molecule-1 were decreased in THC + PPC + losartan animals. In summary, add-on THC to losartan therapy improved antioxidant levels and decreased fibrosis in the kidneys, and lowered blood pressure in diabetic CKD rats.

Comparative analysis of biochemical, hormonal, and mineral compositions of preovulatory and cystic ovarian follicles in buffalo during the non-breeding season.

This study is a comparative analysis of the biochemical, hormonal, and mineral compositions of follicular fluid in preovulatory and cystic follicles of water buffalo (Bubalus bubalis). In total, reproductive tracts from 215 buffalo along with intact ovaries were collected randomly from an abattoir. The incidence of cystic conditions found in this study was 3.72% (8/215), involving the right ovary in 62.5% of instances and the left ovary in 37.5% of instances during the non-breeding season. Follicular fluid was aspirated from preovulatory follicles (12-15 mm diameter, oestrogen-active, follicular phase or stage IV corpus luteum on one of the two ovaries, n = 10) and cystic follicles (at least 20 mm diameter, no corpus luteum on any one of the two ovaries, n = 8). The follicular fluid samples were assayed for biochemical components (uric acid, creatinine, blood urea nitrogen, cholesterol, total protein, glucose, ascorbic acid, and alkaline phosphatase), hormones (progesterone, estradiol, and insulin), and minerals (calcium, magnesium, phosphorus, copper, zinc, and cobalt). Cystic follicles had greater (P < 0.05) concentrations of creatinine, blood urea nitrogen, cholesterol, progesterone, copper, zinc, and cobalt, and lesser (P < 0.05) concentrations of uric acid, glucose, ascorbic acid, estradiol, insulin, calcium, magnesium, and phosphorus compared with preovulatory follicles. These results indicated the marked differences in follicular fluid composition between preovulatory and cystic follicles in buffalo. Some of the changes were indicative of oxidative stress and disturbed steroidogenesis, two important mechanisms shown to be associated with cystic ovarian disease in various species. Further studies are warranted to investigate whether these differences are directly or indirectly involved in the formation of cystic follicles or are mere manifestations of the condition.

Hypobaric hypoxia induced renal injury in rats: Prophylactic amelioration by quercetin supplementation.

The present study aims at assessing the effect of hypobaric hypoxia induced renal damage and associated renal functions in male SD rats. Further, this study was extended to explore the protective efficacy of quercetin in ameliorating the functional impairment in kidneys of rats under hypobaric hypoxia. Rats were exposed to 7620m (25000 ft.) at 25°C ±2 in a simulated hypobaric hypoxia chamber for different time durations (0h,1h, 3h, 6h, 12h, 24h and 48h) in order to optimize the time at which maximum renal damage would occur. The rats were exposed to hypoxia for 12h duration was considered as the optimum time, due to significant increase in oxidative stress (ROS, MDA) and renal metabolites (creatinine, BUN and uric acid) with remarkable reduction (p<0.001) in antioxidants (GSH) in plasma, as compared to other tested durations. Moreover, these findings were in support with the histopathology analysis of renal tissues. For optimum quercetin dose selection, the rats were administered with different doses of quercetin (25mg, 50mg, 100mg and 200mg/Kg BW) for 12h at 7620 m, 25°C ±2, 1h prior to hypoxia exposure. Quercetin 50mg/kg BW was considered as the optimum dose at which significant (p<0.001) reduction in oxidative stress levels followed by reduction in creatinine and BUN levels were obtained in plasma of the rats compared to hypoxia control rats. Quercetin prophylaxis (50mg/kg BW) stabilized the HIF-1α protein expression followed by reduced VEGF protein expression along with reduced levels of LDH (p<0.001) in the kidneys of rats compared to hypoxia control. Histopathological observations further substantiated these findings in reducing the renal tissue injury. The study findings revealed that, quercetin prophylaxis abrogates the possibility of hypobaric hypoxia induced renal injury by reducing the oxidative stress in rats.

Adverse effects of triclosan on kidney in mice: Implication of lipid metabolism disorders.

Triclosan (TCS) is a ubiquitous antimicrobial used in daily consumer products. Previous reports have shown that TCS could induce hepatotoxicity, endocrine disruption, disturbance on immune function and impaired thyroid function. Kidney is critical in the elimination of toxins, while the effects of TCS on kidney have not yet been well-characterized. The aim of the present study was to investigate the effects of TCS exposure on kidney function and the possible underlying mechanisms in mice. Male C57BL/6 mice were orally exposed to TCS with the doses of 10 and 100 mg/(kg•day) for 13 weeks. TCS was dissolved in dimethyl sulfoxide (DMSO) and diluted by corn oil for exposure. Corn oil containing DMSO was used as vehicle control. Serum and kidney tissues were collected for study. Biomarkers associated with kidney function, oxidative stress, inflammation and fibrosis were assessed. Our results showed that TCS could cause renal injury as was revealed by increased levels of renal function markers including serum creatinine, urea nitrogen and uric acid, as well as increased oxidative stress, pro-inflammatory cytokines and fibrotic markers in a dose dependent manner, which were more significantly in 100 mg/(kg•day) group. Mass spectrometry-based analysis of metabolites related with lipid metabolism demonstrated the occurrence of lipid accumulation and defective fatty acid oxidation in 100 mg/(kg•day) TCS-exposed mouse kidney. These processes might lead to lipotoxicity and energy depletion, thus resulting in kidney fibrosis and functional decline. Taken together, the present study demonstrated that TCS could induce lipid accumulation and fatty acid metabolism disturbance in mouse kidney, which might contribute to renal function impairment. The present study further widens our insights into the adverse effects of TCS.

Effect of High Doses of Salep Aqueous Extract on Serum Levels of Urea Nitrogen, Creatinine, Uric Acid, and Kidney Histopathological Changes in Adult Male Wistar Rats.

Kidneys are critical in the clearance and maintenance of active metabolites. One of the medical properties of Salep is treating bladder and kidney inflammation. Due to the widespread use of Salep in traditional medicine and the food industry, and since the effects of Salep on kidney function have not been studied, the present study aimed to investigate the impact of Salep on kidney function. In this experimental study, 48 male rats were divided randomly into six groups as control, sham, and four experimental groups receiving different doses of Salep intraperitoneally (80, 160, 320, and 640 mg/kg). On day 29, after weighing the animals, blood samples were taken from the heart, and serum blood urea nitrogen (BUN), uric acid, and creatinine were analyzed and compared in different groups. All the animal's kidneys were exposed after dissection, and tissue sections were prepared for histopathological evaluation. From day 28 to 29, rats were kept in metabolic cages to collect urine samples and measure water intake and urine volume. The serum concentration of BUN and uric acid in the groups receiving Salep at all doses decreased non-significantly compared to the control group. Furthermore, a significant reduction was seen in creatinine serum levels in groups receiving 320 and 640 mg/kg of Salep extract (P<0.05). No evidence of damage to renal tissue was observed in this study. In conclusion, Salep could decrease serum BUN, uric acid, and creatinine levels due to its antioxidant properties and had no devastating effect on kidneys.

Synthesis, Molecular Docking, and Preclinical Evaluation of a New Succinimide Derivative for Cardioprotective, Hepatoprotective and Lipid-Lowering Effects.

Cardiac and hepatotoxicities are major concerns in the development of new drugs. Better alternatives to other treatments are being sought to protect these vital organs from the toxicities of these pharmaceuticals. In this regard, a preclinical study is designed to investigate the histopathological effects of a new succinimide derivative (Comp-1) on myocardial and liver tissues, and the biochemical effects on selected cardiac biomarkers, hepatic enzymes, and lipid profiles. For this, an initially lethal/toxic dose was determined, followed by a grouping of selected albino rats into five groups (each group had n = 6). The control group received daily oral saline for 8 days. The 5-FU (5-Fluorouracil) group received oral saline daily for 8 days, added with the administration of a single dose of 5-FU (150 mg/kg I.P.) on day 5 of the study. The atenolol group received oral atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5 of the protocol. Similarly, two groups of rats treated with test compound (Comp-1) were administered with 5 mg/kg I.P. and 10 mg/kg I.P. for 8 days, followed by 5-FU (150 mg/kg I.P.) on day 5. Toxicity induced by 5-FU was manifested by increases in the serum creatinine kinase myocardial band (CK-MB), troponin I (cTnI) and lactate dehydrogenase (LDH), lipid profile, and selected liver enzymes, including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total), and BD (direct bilirubin). These biomarkers were highly significantly decreased after the administration of the mentioned doses of the test compound (5 mg/kg and 10 mg/kg). Similarly, histological examination revealed cardiac and hepatic tissue toxicity by 5-FU. However, those toxic effects were also significantly recovered/improved after the administration of Comp-1 at the said doses. This derivative showed dose-dependent effects and was most effective at a dose of 10 mg/kg body weight. Binding energy data computed via docking simulations revealed that our compound interacts toward the human beta2-adrenergic G protein-coupled receptor (S = -7.89 kcal/mol) with a slight stronger affinity than the calcium channel T-type (S = -7.07 kcal/mol). In conclusion, the histological and biochemical results showed that the test compound (Comp-1) had prominent cardioprotective, hepatoprotective, and lipolytic effects against 5-FU-induced toxicity in the subjected animal model.

Effects of pigeon pea leaves and concentrate mixture on feed intake, milk yield, and composition of crossbred dairy cows fed native pasture hay.

Protein supplements are expensive and not easily accessible under small-scale livestock production systems in Ethiopia and other developing countries, which necessitates investigating the alternative protein sources for cost-effective livestock production. Pigeon pea (Cajanus cajan L. Millsp) leaves (PPLs) are rich in protein and are well-suited for feeding small ruminants; however, the effect of inclusion of PPL in the concentrate mixture (CM) on the performance of dairy cows was not well documented. This experiment was conducted to evaluate the effect of supplementation of PPL and CM to native pasture hay-based rations on feed intake, milk yield and composition, and blood metabolites of crossbred dairy cows (Holstein × Zebu). A 4 × 4 Latin square design with three replications, balanced for carryover effects, was used for this study. The treatments included native pasture hay provided ad libitum as a basal diet, supplemented with a CM alone (T1), the inclusion of 10% of PPL in the CM (T2), 20% PPL in the CM (T3), or 30% PPL in the CM (T4). Supplements were isocaloric and isonitrogenous. Total DM intake (hay + supplement intake) was similar (P > 0.05) among treatments. Hay intake was greater (P = 0.05) for T1 and T2 than for T4, while supplement intake was the least for T1 (P < 0.05). The treatment groups T2, T3, and T4, where PPL was included, had similar (P > 0.05) supplement intake. Feed intake, milk yield and composition, feed conversion efficiency, body condition score, serum total protein, albumin, globulin, glucose, triglyceride, urea N, creatinine, and cholesterol were similar (P > 0.05) among treatments. The inclusion of up to 30% of PPL in the CM resulted in a comparable performance of crossbred dairy cows as supplementation with CM under the conditions of the current experiment. Therefore, further study is required to evaluate the effect of the inclusion of a higher level of PPL in the concentrate mixture on the performance of lactating crossbred dairy cows.

Ethanol extract of Nepeta angustifoia C. Y. Wu ameliorates hyperuricemia in fructose-induced mice.

As a popular medicinal plant traditionally used in Tibet of China, Nepeta angustifolia C. Y. Wu is mainly administered to treat apoplexia, cerebral haemorrhage, fainting and epilepsy and other symptoms, while its effect on hyperuricemia is still unclear. In the present study, we evaluated the improvement of the 70% ethanol extract of Nepeta angustifolia C. Y. Wu in fructose-induced hyperuricemic mice. The results revealed that Nepeta angustifolia C. Y. Wu significantly decreased blood glucose and blood lipid levels, as well as lowering the urinary levels of uric acid, creatinine and urea nitrogen. Meanwhile, it effectively restored the serum levels of uric acid, creatinine and urea nitrogen and inhibited serum and hepatic XOD activities and renal oxidative stress, while suppressing the secretions of TNF-α, IL-1ß and IL-6 in kidney. Nepeta angustifolia C. Y. Wu also attenuated the infiltration of inflammatory cells and reduced the production and accumulation of glycogen and collagen, while restoring the dysregulated protein expressions of renal URAT1, GLUT9, OAT1 and OAT3. In summary, our results support the idea that Nepeta angustifolia C. Y. Wu is a promising agent for treating hyperuricemia.

Anti-inflammatory potential of stevia residue extract against uric acid-associated renal injury in mice.

Abnormal uric acid level result in the development of hyperuricemia and hallmark of various diseases, including renal injury, gout, cardiovascular disorders, and non-alcoholic fatty liver. This study was designed to explore the anti-inflammatory potential of stevia residue extract (STR) against hyperuricemia-associated renal injury in mice. The results revealed that STR at dosages of 150 and 300 mg/kg bw and allopurinol markedly modulated serum uric acid, blood urea nitrogen, and creatinine in hyperuricemic mice. Serum and renal cytokine levels (IL-18, IL-6, IL-1Β, and TNF-α) were also restored by STR treatments. Furthermore, mRNA and immunohistochemistry (IHC) analysis revealed that STR ameliorates UA (uric acid)-associated renal inflammation, fibrosis, and EMT (epithelial-mesenchymal transition) via MMPS (matrix metalloproteinases), inhibiting NF-κB/NLRP3 activation by the AMPK/SIRT1 pathway and modulating the JAK2-STAT3 and Nrf2 signaling pathways. In summary, the present study provided experimental evidence that STR is an ideal candidate for the treatment of hyperuricemia-mediated renal inflammation. PRACTICAL APPLICATIONS: The higher uric acid results in hyperuricemia and gout. The available options for the treatment of hyperuricemia and gout are the use of allopurinol, and colchicine drugs, etc. These drugs possess several undesirable side effect. The polyphenolic compounds are abundantly present in plants, for example, stevia residue extract (STR) exert a positive effect on human health. From this study results, we can recommend that polyphenolic compounds enrich STR could be applied to develop treatment options for the treatment of hyperuricemia and gout.

Magnesium Lithospermate B Protects Against Cisplatin-Induced Acute Kidney Injury via Alleviating Mitochondrial Dysfunction.

Purpose: Apoptosis plays a critical role in cisplatin-induced acute kidney injury (AKI) and is related to mitochondrial dysfunction. Magnesium lithospermate B (Mlb), one of the most important components of Salvia miltiorrhiza Bunge, is mainly used to treat cardiovascular diseases because of its anti-apoptotic effects. The mechanism underlying the protective effect of Mlb against cisplatin-induced AKI remains unclear. In this study, we investigated the protective effect of Mlb on mitochondrial function against apoptosis caused by cisplatin-induced renal injury. Methods: Renal injury induced by cisplatin in mouse renal tubular epithelial cells (mTECs) was measured by quantifying serum creatinine levels, mitochondrial morphology, cell viability, apoptosis, Dynamin-related protein 1(Drp1) expression, etc. The cells were then administered Mlb to determine its protective effects against cisplatin-induced AKI. Results: Mlb treatment significantly reduced serum creatinine levels and pathological injury of renal, inhibited the production of malondialdehyde, and reduced the depletion of superoxide dismutase. In addition, Mlb reduced Bax/Bcl2, cleaved caspase-3/caspase-3, and maintained mitochondrial integrity after AKI. Mlb administration also improved cell viability and reduced the percentage of apoptotic cells in vitro. Furthermore, Mlb reduced mitochondrial reactive oxygen species, improved mitochondrial membrane potential, and ameliorated mitochondrial morphological abnormalities by downregulating Drp1 expression. Conclusion: These results indicated that Mlb could protect the kidneys against cisplatin-induced apoptosis by alleviating mitochondrial dysfunction.

3-Indolepropionic acid prevented chlorpyrifos-induced hepatorenal toxicities in rats by improving anti-inflammatory, antioxidant, and pro-apoptotic responses and abating DNA damage.

The application of chlorpyrifos (CPF), an organophosphorus pesticide to control insects, is associated with oxidative stress and reduced quality of life in humans and animals. Indole-3-propionic acid (IPA) is a by-product of tryptophan metabolism with high antioxidant capacity and has the potential to curb CPF-mediated toxicities in the hepatorenal system of rats. It is against this background that we explored the subacute exposure of CPF and the effect of IPA in the liver and kidney of thirty rats using five cohort experimental designs (n = 6) consisting of control (corn oil 2 mL/kg body weight), CPF alone (5 mg/kg), IPA alone (50 mg/kg), CPF + IPA1 (5 mg/kg + 25 mg/kg), and CPF + IPA2 (5 mg/kg + 50 mg/kg). Subsequently, we evaluated biomarkers of hepatorenal damage, oxidative and nitrosative stress, inflammation, DNA damage, and apoptosis by spectrophotometric and enzyme-linked immunosorbent assay methods. Our results showed that co-treatment with IPA decreased CPF-upregulated serum hepatic transaminases, creatinine, and urea; reversed CPF downregulation of SOD, CAT, GPx, GST, GSH, Trx, TRx-R, and TSH; and abated CPF upregulation of XO, MPO, RONS, and LPO. Co-treatment with IPA decreased CPF-upregulated IL-1ß and 8-OHdG levels, caspase-9 and caspase-3 activities, and increased IL-10. In addition, IPA averts CPF-induced histological changes in the liver and kidney of rats. Our results demonstrate that co-dosing CPF-exposed rats with IPA can significantly decrease CPF-induced oxidative stress, pro-inflammatory responses, DNA damage, and subsequent pro-apoptotic responses in rats' liver and kidneys. Therefore, supplementing tryptophan-derived endogenous IPA from exogenous sources may help avert toxicity occasioned by inadvertent exposure to harmful chemicals, including CPF-induced systemic perturbation of liver and kidney function.

Effect of Hydroaloholic Extract of Rotula Aquatica Lour on Gentamicin-Induced Nephrotoxicity in Wistar Albino Rats: An In Vitro and In Vivo Approach.

One-third of the world population suffer from kidney complications such as acute and chronic renal failure, renal calculi, kidney stones, Fanconi's syndrome and urethritis which doesn't have a proper effective treatment regimen. The current study explores the nephroprotective effect of herbal drug Rotula Aquatica by both In Vitro and In Vivo methods. MTT assay was applied In Vitro to evaluate the nephroprotective effect of R. aquatica leaves extract on HEK 293 cell line. The acute toxicity of the extract was evaluated as per the limit test under the protocol of OECD 423 at a concentration of 2000 mg/kg using 6 female rats. Further, an In Vivo study using the Gentamicin-instigated nephrotoxicity model was carried out for a period of 8 days. Biochemical markers of renal damage, endogenous antioxidants and histopathology were determined to assess the effect of treatment. The In Vitro study using HEK 293 cell line resulted in an EC50 value of 51.50 µg/ml for the extract in comparison to the standard drug Cytsone (12.26 µg/ml). Based on the limit test of OECD 423, doses of 200 and 400 mg/kg were chosen for the study. The results revealed a strong nephroprotective activity at 400 mg/kg in Gentamicin-induced nephrotoxicity against standard drug cystone by restoring the decrement in body weight, renal enzymatic and non-enzymatic antioxidants, creatinine and urea levels in urine and plasma. This indicated that hydroalcoholic extract of Rotula aquatica (HAERA) can prevent the Gentamicin toxicity due to the high content of antioxidant and anti-inflammatory secondary metabolites.

Protective effect of bee pollen in acute kidney injury, proteinuria, and crystalluria induced by ethylene glycol ingestion in rats.

Oxidative stress plays a role in hyperoxaluria-induced kidney injury and crystallization. Bee pollen is a hive product with a high content of antioxidants. The antioxidant content and protective effect of bee pollen extract (BPE) against ethylene glycol (EG) induced crystalluria, and acute kidney injury (AKI) were investigated. The effect of BPE on the EG-induced liver injury and proteinuria was also examined. Ten groups of male Wister rats were treated daily with vehicle, cystone, BPE (100, 250, and 500 mg/kg b.wt.), and group 6-9 treated with EG, EG + BPE (100, 250, and 500 mg/kg b.wt.) and group 10 EG + cystone. The dose of EG was 0.75% v/v, and the dose of cystone was 500 mg/kg b.wt. On day 30, blood and urine samples were collected for analysis. Kidneys were removed for histopathological study. The antioxidant activity of BPE was assessed, and its total phenols and flavonoids were determined. EG significantly increased urine parameters (pH, volume, calcium, phosphorus, uric acid, and protein), blood urea, creatinine, and liver enzymes (P < 0.05). EG decreased creatinine clearance and urine magnesium and caused crystalluria. Treatment with BPE or cystone mitigates EG's effect; BPE was more potent than cystone (P < 0.05). BPE increases urine volume, sodium, and magnesium compared to the control and EG treated groups. BPE reduces proteinuria and prevents AKI, crystalluria, liver injury, and histopathological changes in the kidney tissue caused by EG. BPE might have a protective effect against EG-induced AKI, crystalluria, proteinuria, and stone deposition, most likely by its antioxidant content and activity.