scholarly journals 5-aminoisoquinoline improves renal function and fibrosis during recovery phase of cisplatin-induced acute kidney injury in rats

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Andrés Quesada ◽  
Francisco O’Valle ◽  
Sebastián Montoro-Molina ◽  
Mercedes Gómez-Morales ◽  
Mercedes Caba-Molina ◽  
...  

The aim of the present study is to analyze the effects of 5-aminoisoquinoline (5-AIQ), a poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, over renal dysfunction and fibrosis during recovery phase of cisplatin (CisPt)-induced acute kidney injury (AKI) in rats. Male Wistar rats were distributed in three groups (n=8 each group): control, CisPt, and CisPt + 5-AIQ. Control and CisPt groups received a subcutaneous injection of either saline or 7 mg/kg CisPt, respectively. CisPt + 5-AIQ group received two intraperitoneal injections of 10 mg/kg 5-AIQ 2 h before and 24 h after CisPt treatment. Thirteen days after the treatment, rats were housed in metabolic cages and 24-h urine collection was made. At day 14, CisPt-treated rats showed increased diuresis, N-acetyl-β-d-glucosaminidase (NAG) excretion, glucosuria and sodium fractional excretion (NaFE), and decreased creatinine clearance (CrCl). 5-AIQ significantly increased CrCl and decreased NAG excretion, glucosuria, and NaFE. In plasma, CisPt increased sodium, urea, and creatinine concentrations, while 5-AIQ treatment decreased these variables to the levels of control group. 5-AIQ completely prevented the body weight loss evoked by CisPt treatment. CisPt also induced an increased renal expression of PAR polymer, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and collagen-IV. These variables were decreased in CisPt + 5-AIQ group. Tubular lesions and renal fibrosis were also decreased by 5-AIQ treatment. We conclude that inhibition of PARP1 with 5-AIQ can attenuate long-term nephrotoxic effects associated with the CisPt treatment, preventing renal dysfunction and body weight decrease and ameliorating tubular lesions and collagen deposition.

2017 ◽  
Vol 43 (5) ◽  
pp. 1841-1854 ◽  
Author(s):  
Jun Zhou ◽  
Jiying  Zhong ◽  
Sen  Lin ◽  
Zhenxing Huang ◽  
Hongtao Chen ◽  
...  

Background: Renal fibrosis is a common pathophysiological feature of chronic kidney disease. Acute kidney injury (AKI) is defined as an independent causal factor of chronic kidney disease, with a pathological representation of post renal fibrosis. However, the etiopathogenesis underlying post renal fibrosis induced by AKI is not completely understood. Methods: BALB/c mice were treated with bpv or vehicle controls and were, respectively, the ischemia reperfusion (IR) model group and control group. All of the animals had blood taken from the orbital venous plexus at 24 hours after IR. Six mice in each group were randomly chosen and euthanized 7 days after IR treatment, and the remaining six mice in each group were euthanized 14 days after IR treatment. We examined the effect on post kidney fibrosis of inhibiting PTEN activity in mice in an IR induced AKI experimental model. Results: Compared with vehicle mice, bpv-(PTEN specific inhibitor) treated mice accumulated more bone marrow-derived fibroblasts and myofibroblasts in the kidneys. Inhibition of PTEN activity increased the expression of α-smooth muscle actin and extracellular matrix proteins and post kidney fibrosis. Furthermore, inhibition of PTEN activity resulted in more inflammatory cytokines in the kidneys of mice subjected to IR-induced renal fibrosis. Moreover, inhibition of PTEN activity up-regulated PI3K protein expression and Akt phosphorylation. Conclusions: Our study demonstrated that PTEN played an important role in post renal fibrosis in mice with ischemia reperfusion-induced AKI. These results indicated that the PTEN/PI3K/Akt signaling pathway may serve as a novel therapeutic target for AKI-induced chronic kidney disease.


1976 ◽  
Vol 29 (4) ◽  
pp. 341 ◽  
Author(s):  
VJ Williams ◽  
W Senior ◽  
JilI Sippel

Sixteen female rats aged about 80 days and with a mean body weight of 175 g were fed 40 % of their ad libitum intake of a laboratory chow. They were killed and analysed for water, protein, lipid and ash after 9, 21� 5, 30� 2 and 38�8 % of body weight had been lost. Compared to a control group of four animals, the 38�8 % group lost 13 g or 34 % of their protein. The animals in the 21 . 5, 30� 2 and 38 . 8 % groups lost 7� 5 g or 87 % of their lipid leaving only 1 �1 g of lipid. The percentage protein in the body was little affected by body weight loss but lipid decreased from 5 to 1 %. In another experiment with 26 rats of 205 g mean body weight and aged about 115 days, absorption rates by the small intestine were measured in vivo after variable weight losses between 0 and 39 %. o( + )-Glucose uptake was increased by about 70 % in those animals which had lost only 5 % of body weight and this increased uptake was retained in those rats which had lost up to 39 % of body weight. The absorption of L-leucine was not affected by the decline in body weight compared to the controls but relative to body weight, the ability of the intestine to absorb increased. In the same animals, the wet and dry weights of the small intestine declined slightly faster than body weight and the length of the small intestine tended to decrease slightly with increasing loss of body weight.


Author(s):  
Dayo Rotimi Omotoso ◽  
Adeniran Oluwadamilare Akinola ◽  
Ibifuro Brown

To assess the effect of methanolic leaf extract of Caladium bicolor on the histomorphology of gastrointestinal tissues of experimental animals. Twenty four Wistar rats (weighing between 175-190 g) were randomly and equally divided into four groups which include one control group (CG) and three treatment groups (TG I, TG II and TG III). The CG was administered with distilled water [2 ml/kg body weight (b.w.)] while TGs I, II and III were administered with 100 ml/kg, 200 ml/kg and 300 ml/kg (b.w.) of C. bicolor extract respectively. All administrations were done orally and once daily for a period of thirty days. The body weight of all animals was recorded at the beginning and end of study. After the period of study, gastric and small intestinal tissues of experimental animals were harvested, processed, converted to tissue blocks and sectioned. Tissue sections were stained using Haematoxylin and Eosin (H&E) technique. Thereafter, stained sections microscopically examined for observable histopathological changes within study tissues. The results of this study showed that exposure to C. bicolor extract causes significant (p < 0.05) body weight loss in TGs I-III compared to CG. In addition, prominent histopathological changes were observed in gastrointestinal tissues of experimental animals in TGs I-III including gastric mucosal surface erosion and intestinal villi degeneration compared to normal gastrointestinal histomorphology of CG animals. These histopathological changes may be associated with toxic effect of phytochemicals constituents of the extract. Therefore, its application for therapeutic purposes needs to be thoroughly re-validated or perhaps disallowed where alternative therapeutic agents with minimal toxic potential exist.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sheng Zhang ◽  
Chao Li ◽  
Tingting Feng ◽  
Shuai Cao ◽  
Heng Zhou ◽  
...  

Realgar has been used as a type of mineral drug that contains arsenic for thousands of years. Previous studies have shown that Realgar-induced acute kidney injury is associated with abnormal metabolism, but the underlying mechanism is poorly understood. The aim of this study is to investigate the metabolic changes in serum and kidney tissues of mice exposed to Realgar by using a metabolomic approach and explore the molecular mechanisms of acute kidney injury induced by Realgar. Forty mice were randomly divided into four groups: Control group, 0.5-, 1.0, and 2.0 g/kg Realgar group. After 1 week, the body weight and kidney weight of the mice were measured. The serum and kidney samples were used for LC-MS spectroscopic metabolic profiling. Principal component analysis (PCA), correlation analysis, and pathway analysis were used to detect the nephrotoxic effects of Realgar. Body weight decreased significantly in the 2.0 g/kg group, and the kidney weight index also showed a dose-dependent increase in Realgar. The PCA score plot showed the serum and kidney tissue metabolic profile of mice exposed to 2.0 g/kg Realgar separated from the control group, while the lower-doses of 0.5 g/kg and 1.0 g/kg Realgar shown a similar view to the Control group. Thirty-three metabolites and seventeen metabolites were screened and identified in the serum and kidney of mice in a dose-dependent manner. respectively. Correlation analysis showed a strong correlation among these metabolites. Amino acid metabolism, lipid metabolism, glutathione metabolism, and purine metabolism pathways were found to be mainly associated with Realgar nephrotoxicity. This work illustrated the metabolic alterations in Realgar-induced nephrotoxic mice through a metabolomic approach.


2020 ◽  
pp. 335-343
Author(s):  
Claude Mona Airin ◽  
Amelia Hana ◽  
Sarmin ◽  
Pudji Astuti ◽  
Amir Husni ◽  
...  

Thyroxine hormone (T4) was one of the hormones related to metabolism rate. Animal transportation could be stressor interfering metabolism. Sargassum crasifoium was one of brown algae species that contained some important nutrients and also flavonoids. The study aimed at finding out the effect of the Sargassum on the decrase in thyroxine hormone and body weight loss. It used 9 Javanese Randu goats that were classified into 3 treatment groups. Group I served as control, Group II was treated with 450 mg/kg BW of Sargassum estract and Group III was treated with vitamin B1. All of the goats were transported for 12 hours using pickup truck at the speed of 60 km/hour. Blood samples were drawn before the transportation, during loading, 6 hours after the transportation and at the end of the transportation, while the body weight of the goats was weighed before and after the transportation. The results of the study showed that the T4 hormone decreased in the Group I and increased in the Group III during the transportation, while it was stable in the Group II. The biggest percentage of the body weight loss took place to the Group III (0.13%), while the smallest percentage took place to the Group II (0.063%). Statistical analysis showed that the Sargassum extract did not have any significant effect (p>0.05) on both the thyroxine hormone and the body weight loss during the transportation. Based on the results of the study it could be concluded that the Sargassum extract could stabilize the thyroxine hormone during the transportation so that it could prevent the body weight loss


2022 ◽  
Author(s):  
Leticia Urbano Cardoso Castro ◽  
Denise Aya Otsuki ◽  
Talita Rojas Sanches ◽  
Felipe Lima Souza ◽  
Mirela Aparecida Rodrigues Santinho ◽  
...  

Abstract Hemorrhagic shock (HS), a major cause of trauma-related mortality, is mainly treated by crystalloid fluid administration, typically with lactated Ringer’s (LR). Despite beneficial hemodynamic effects, such as the restoration of mean arterial pressure (MAP), LR administration has major side effects, including organ damage due to edema. One strategy to avoid such effects is pre-hospitalization intravenous administration of the potent vasoconstrictor terlipressin, which can restore hemodynamic stability/homeostasis and has anti-inflammatory effects. Wistar rats were subjected to HS for 60 min, at a target MAP of 30–40 mmHg, thereafter being allocated to receive LR infusion at 3 times the volume of the blood withdrawn; at 2 times the volume, plus terlipressin (10 µg/100 g body weight); and at an equal volume, plus terlipressin (10 µg/100 g body weight). A control group comprised rats not subjected to HS and receiving no fluid resuscitation or treatment. At 15 min after fluid resuscitation/treatment, the blood previously withdrawn was reinfused. At 24 h after HS, MAP was higher among the terlipressin-treated animals. Terlipressin also improved post-HS survival and provided significant improvements in glomerular/tubular function (creatinine clearance), neutrophil gelatinase-associated lipocalin expression, fractional excretion of sodium, aquaporin 2 expression, tubular injury, macrophage infiltration, IL-6 levels, IL-18 levels, and NF-κB expression. In terlipressin-treated animals, there was also significantly higher ANG II type 1 receptor expression and normalization of AVP 1a receptor expression. Terlipressin could be a viable therapy for HS-induced acute kidney injury, likely attenuating such injury by modulating the inflammatory response via the AVP 1a receptor.


2014 ◽  
Vol 84 (1-2) ◽  
pp. 5-11 ◽  
Author(s):  
Eun Y. Jung ◽  
Sung C. Jun ◽  
Un J. Chang ◽  
Hyung J. Suh

Previously, we have found that the addition of L-ascorbic acid to chitosan enhanced the reduction in body weight gain in guinea pigs fed a high-fat diet. We hypothesized that the addition of L-ascorbic acid to chitosan would accelerate the reduction of body weight in humans, similar to the animal model. Overweight subjects administered chitosan with or without L-ascorbic acid for 8 weeks, were assigned to three groups: Control group (N = 26, placebo, vehicle only), Chito group (N = 27, 3 g/day chitosan), and Chito-vita group (N = 27, 3 g/day chitosan plus 2 g/day L-ascorbic acid). The body weights and body mass index (BMI) of the Chito and Chito-vita groups decreased significantly (p < 0.05) compared to the Control group. The BMI of the Chito-vita group decreased significantly compared to the Chito group (Chito: -1.0 kg/m2 vs. Chito-vita: -1.6 kg/m2, p < 0.05). The results showed that the chitosan enhanced reduction of body weight and BMI was accentuated by the addition of L-ascorbic acid. The fat mass, percentage body fat, body circumference, and skinfold thickness in the Chito and Chito-vita groups decreased more than the Control group; however, these parameters were not significantly different between the three groups. Chitosan combined with L-ascorbic acid may be useful for controlling body weight.


2020 ◽  
Vol 16 (8) ◽  
pp. 1270-1277
Author(s):  
Hiba F. Al-Sayyed ◽  
Hamed R. Takruri ◽  
Nawal A. Bakir ◽  
Dima H. Takruri

Background : Female menstrual changes in hormone concentration influence appetite and eating behavior. As well, eating pattern has some influences on menstrual hormonal status. Feeding date palm fruit has been found in our previous report to affect menstrual hormones and some menstrual parameters. Objective: The aim of this research is to study the effect of feeding dates on energy, macronutrient, and fiber intakes, body weight, and body fat%. Additionally, this study aims to find any correlation between menstrual hormone concentration and the above-mentioned parameters. Methods: A convenient sample (n=37) of not-sexually active females aged 20-30 were divided into two groups; one group (dates group) was fed 7 dates and the other served as a control group. The participants of the control group were exposed to the same experimental conditions except for eating dates. Throughout the feeding trial, the volunteers filled a 3-day food record; one menses day and two non-menses days. Results: There was a significant effect of the menstrual status-feeding duration interaction in terms of protein and fat intakes. Additionally, menstrual status, as well as feeding duration, affected energy and macronutrient intakes significantly. Furthermore, feeding duration affected fiber intake significantly. Despite the above-mentioned differences in energy and macronutrient intakes, these effects didn’t affect the body weight and body mass index of the study participants, neither their body fat%. Moreover, we have found significant correlations between nutrient intakes and menstrual hormone concentration. Conclusion : Feeding dates affected energy, macronutrient, and fiber intakes significantly. These effects were related to the changes in menstrual hormone concentration.


2019 ◽  
Vol 15 (02) ◽  
pp. 14-17
Author(s):  
K K Hadiya ◽  
A J Dhami ◽  
D V Chaudhari ◽  
P M Lunagariya

This study was initiated on 24 prepubertal Holstein x Kankrej crossbred heifers of nearly identical age (7-9 months) and body weight (130-140 kg) at University farm to evaluate the effect of high plane of nutrition on blood biochemical and minerals profile and the age at puberty. Twelve heifers were managed under routine farm feeding (control) and the rest 12 under ideal optimum feeding regime (treatment) that included extra 1 kg concentrate, 30 g min mix and ad-lib dry fodder. The body weight and ovarian ultrasonography together with blood sampling was carried out at monthly interval from 10 to 18 months of age to study the ovarian dynamics and blood biochemical changes. High plane of nutrition to growing heifers was beneficial in reducing the age of onset of puberty (by 2-3 months) compared to routine farm fed group. The mean plasma total protein and cholesterol concentrations showed a rising trend with significant variations from 10 to 16 months of age, where it got mostly stabilized indicating adult profile. The activity of enzymes GOT and GPT also rose gradually and significantly from 10 months till 14-15 months of age, and thereafter it remained more or less static till 18 months of age. The levels of both these enzymes were higher, with lower protein and cholesterol, in control than the treatment group from 15-16 months of age onwards. The mean plasma levels of both calcium and phosphorus increased gradually and significantly with advancing age till 16-17 months of age, with little higher values in supplemented than a control group. The plasma levels of zinc, iron, copper, and cobalt also showed rising trend with significant differences between 10th and 12th-14th months of age, and from 15th to 18th months of age the levels were statistically the same in all the groups with slightly higher values in the treatment group.


Sign in / Sign up

Export Citation Format

Share Document