Kidneys Of Animals Research Articles

NEPHROPROTECTIVE EFFECT OF DIOSPYROS MALABARICA (DESR.) KOSTEL AGAINST CISPLATIN INDUCED NEPHROTOXICITY IN RATS

The plant Diospyros malabarica (Desr.) Kostel are such plant, which are abundantly grown and various parts are traditionally used for treating wound, cancer, diabetes, ulcer, diarrhea, and renal diseases. Further, it was observed that there is no pharmacological standard established on fruits of Diospyros malabarica (Desr.) Kostel. The present investigation was designed to evaluate the ability of ethanolic extract of fruits of Diospyros malabarica (Desr.) Kostel to combat cisplatin (7.5 mg/kg, i. p.) induced nephrotoxicity. The protective property of ethanolic extract of fruits of Diospyros malabarica (Desr.) Kostel was assessed by measuring the body weight of animals before and after experiments, calculating change in body weight of animals, weight of kidney, urine output and estimating urine creatinine, serum creatinine, blood urea, blood urea nitrogen and histopathological observations of kidney. Our data showed that, cisplatin administration resulted in significant increased biochemical parameters levels. Pretreatment with ethanolic extract of fruits of Diospyros malabarica (Desr.) Kostel normalized the cisplatin induced biochemical parameters levels, protected the rat kidneys from cisplatin induced histopathological changes, restored body weight reduction and prevent increase in weight of kidney of animals. The ethanolic extract of fruits of Diospyros malabarica (Desr.) Kostel offered commendable protection against cisplatin induced nephrotoxicity and possible mechanism underlying this effect is mediated collectively through presence of polyphenols like flavonoids, tannins, higher urine output and antioxidant effect. The present study gives the idea that when we use the plant along with the cisplatin, will reduce the incidence of drug induced nephrotoxicity.

Organ Transportation Thermoelectric Cooling System Design and Application

Thermoelectric modules are used in medical devices, air conditioners, refrigeration cabinets, measuring devices, etc. widely used in the fields. Application areas of thermoelectric modules and efforts to increase efficiency are in continuous development. In this study, an organ transport device with the thermoelectric cooling feature, which can be used in the medical field, was designed and performed and performance analyzes were made. An animal kidney measuring 5x6x10 cm was placed in the designed and realized system, and performance analyzes of the system were made at ambient temperatures of 25ºC, 30ºC, 35ºC, 40ºC. Each experiment was repeated five times and the average was taken. It was seen that the system, whose performance analyzes were carried out at different temperatures, was usable. The system's small size, less weight and low cost compared to conventional cooling systems are among the important advantages of the system. It is possible to say that with the further development of the implemented system, larger organs can be cooled and transported and further studies can be carried out in this direction.

Interleukin-6 mediates lipopolysaccharide-inhibited irisin secretion in Nile tilapia (Oreochromis niloticus)

Irisin is a novel immunomodulatory adipomyokine released upon cleavage of the fibronectin type III domain-containing protein 5 (FNDC5). We aimed to examine interleukin-6 (IL-6) role in mediating irisin secretion in immunologically challenged animal and primary head kidney leukocytes cultured from tilapia. Intraperitoneal injection of lipopolysaccharide (LPS) increased plasma IL-6 levels and decreased irisin secretion, suggesting a causal relationship between the induction of IL-6 and irisin. To address this relationship, we further produced recombinant tilapia IL-6 and the anti-tilapia IL-6 polyclonal antiserum. Intraperitoneal injection of recombinant tilapia IL-6 inhibited plasma irisin levels. Consistent with this observation, LPS-induced inhibition of plasma irisin was significantly attenuated by neutralizing circulating IL-6 using an IL-6 antiserum. Besides, IL-6 treatment could inhibit irisin secretion and FNDC5 gene expression in primary cultures of tilapia head kidney leukocytes. In parallel experiments, both LPS and IL-6 blockade of irisin secretion could be reverted by IL-6 receptor antagonism. At the level of the leukocyte, IL-6 treatment also triggered rapid phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), whereas IL-6-reduced irisin secretion could be negated by inhibiting the JAK2 and STAT3 signaling pathways. These results, as a whole, provide the first evidence that IL-6 is the mediator of LPS-inhibited irisin secretion via activation of the JAK2/STAT3 signaling pathway.

Spondias mombin leaf extract ameliorates cerebral ischemia/reperfusion-induced cardiohepatorenal oxidative stress in rats

BackgroundStroke remains a leading cause of mortality and morbidity worldwide. Ischemic stroke is the most prevalent type of stroke and it is characterized by increased oxidative stress and other pathophysiological processes resulting from the reduction of blood flow to the brain. Medicinal plants have been reported to protect against oxidative stress and possess therapeutic potential for the management of stroke. In particular, Spondias mombin leaf extracts have been reported to possess antioxidant and neuroprotective properties. However, the ability of Spondias mombin leaf extract to protect distant organs against ischemicstroke mediated oxidative stress is not yet established. This study therefore evaluated the protective effects of Spondias mombin leaf extract (SML) on bilateral common carotid artery occlusion/reperfusion (BCCAO/R) ischemicstroke model-induced cardiac, hepatic, and renal oxidative stress in rats. MethodMale Wistar rats underwent 30 min of BCCAO and 24 h of reperfusion. Some groups of animals were post-treated with SML (25–100 mg/kg) or quercetin (20 mg/kg). Markers of oxidative stress were evaluated in the heart, liver, and kidney of the experimental animals. ResultsBCCAO/R significantly (p < 0.0001) induced oxidative stress in the heart, liver, and kidney of rats. This was reflected in decreased superoxide dismutase activity and reduced glutathione level. Also, there was increased lipid peroxidation, elevated nitric oxide level, and increased activity of myeloperoxidase. Post-treatment with SML significantly (p < 0.05) ameliorated BCCAO/R-induced oxidative stress in all the organs. ConclusionsCerebral ischemia/reperfusion significantly induced oxidative stress in the heart, liver, and kidney of rats and Spondias mombin leaf extract showed appreciable therapeutic potential against post-stroke cardiohepatorenal oxidative damage.

Risk Profiling of Fumonisin in Corn (Zea mays L.) to the Filipino Consuming Population

The Fusarium fungus is known to produce fumonisin, a naturally occurring mycotoxin associated with chronic adverse health effects in animal liver and kidney, which is commonly found in corn (Zea mays L.), one of the major agricultural crops and staple foods in the Philippines. The objective of this study was to develop a profile of the potential risks associated with the consumption of corn contaminated with fumonisins B1 (FB1) and B2 (FB2). This study involved the determination of data gaps in the risk profiling process; identification, and characterization of fumonisin; estimation of the dietary exposure (DE) and risk based on identified uncertainties, variabilities, and assumptions; and determination of available risk management options for fumonisin in corn. Fumonisin levels of corn samples (n = 77) were all below the 4000 μg/kg maximum level (ML) set in the 2019 edition of the Codex General Standard for Contaminants and Toxins in Foods (Codex GSCTFF) for raw corn grains. At the 97.5th percentile consumption of corn [yellow, white, green (or sweet) corn; edible portions (corn kernels)], the calculated DE estimates of the Filipino adult (20–59 yr old) exceeded the provisional maximum tolerable daily intake (PMTDI) of 2 μg/kg bw (body weight)/d by 420.17% (maximum FB1), 194.30% (maximum FB2), and 189.81% (overall FB1 mean). Considering the assumptions made and the gathered data in this study, the estimated DE to fumonisin in corn showed an appreciable risk to health. The current ML of fumonisin in corn and corn products adopted from Codex GSCTFF may be in need to be revisited to ensure the protection of the adult Filipino consuming population.

Detection of infection with hydatid cysts in abattoirs animals at Kirkuk governorate, Iraq

During the period from September 2020 to February 2021, the current study was conducted to determine the total prevalence of infection with hydatid cysts disease in the various organs (especially liver, lung, spleen, kidney, heart, and mesentery) of abattoirs animals (sheep, cattle, goats and buffaloes) in Kirkuk governorate and its suburbs. Visual examination and hand-feeling were used to detect and identify the site of infection with hydatid cysts, as well as a microscopic examination was used to determine the fertility of hydatid cysts.&#x0D; A total of 4122 abattoirs animals were examined, including: 1860 sheep, 1550 cattle, 680 goats and 32 buffaloes. The hydatid cysts was found in 133 animal samples (42 sheep, 83 cattle, 6 goats and 2 buffaloes), the total prevalence of infection was 2.25%, 5.35%, 0.88%, 6.25% in sheep, cattle, goats and buffaloes, respectively. The prevalence of infection in females of abattoirs animals was more than in males, which was 0.48%, 1.77% in sheep; 1.48%, 3.87% in cattle; 0.29%, 0.58% in goats, for male and female respectively. While, the prevalence of infection was 6.25% in females of buffaloes compared with their males which didn’t infected.&#x0D; The results showed that the liver is the most organ of the animal’s body to be infected with hydatid cyst, the prevalence of infection in the liver of males and females was 63.63%, 44.44% in sheep, 46.66%, 65.21% in cattle, 50.00%, 50.00% in goats and 0.00%, 50.00% in buffaloes, respectively.&#x0D; The infection with fertile hydatid cysts in sheep, especially in livers of females (80.95%) is higher compared with other infections of abattoirs animals, while it was noticed that the highest prevalence of sterile hydatid cysts in the lungs of females cattle (93.33%). In addition, the most cases of calcified hydatid cysts were observed in the lungs of females sheep (50.00%) and livers of females cattle (32.14%).

Abstract 9552: RNA Sequencing of Cardiac and Renal Tissue in a Rat Model of Chronic Kidney Disease Reveals Chronodisruption as Common Pathway

Introduction: Chronic kidney disease (CKD) is often accompanied by cardiovascular disease, which is referred to as type 4 cardiorenal syndrome. Management is challenging due to the multifactorial nature of the condition, and treatment of one organ may negatively impact the other. Hypothesis: More insights into the common molecular disease processes in the heart and kidney might provide a source for new therapies. We used RNA sequencing to identify pathways that were dysregulated in both organs. Methods: Cardiac and renal tissue samples from four 5/6 th partial nephrectomized (NX) and four sham-operated (SHAM) female Sprague-Dawley rats were analyzed using RNA sequencing. Strand-specific and rRNA depleted cDNA libraries were generated and were sequenced on NovaSeq (Ilumina) with 20 million reads per library. Results: In comparison to SHAM, the kidneys of NX animals had 290 differentially expressed genes (DEGs), showing increased expression of genes that map to Gene Ontology terms including collagen fibril organization , circadian regulation of gene expression , mitotic cell cycle , neutrophil chemotaxis , and inflammatory response . Within the hearts of NX animals, 8 DEGs were found, including those related to circadian regulation of gene expression (Per2, Per3, Arntl/Bmal1, BHLHE41) , as well as the Adra1d , C2cd4b , Ubtd1 , and Atp2b2 genes. Four genes were differentially expressed in both organs. Three of them were related to circadian rhythm, with Per2 and Per3 being downregulated and Arntl/Bmal1 being upregulated. Furthermore, Adra1d was downregulated in both organs. Conclusions: This comprehensive RNA sequencing in a rat model of type 4 cardiorenal syndrome identified chronodisruption as a common pathway, suggesting that circadian rhythms could be a novel target for intervention. Figure Legend. (A) Venn diagram with number of DEGs and vulcano plots for heart (left) and kidney (right). (B) GO terms for heart. (C) GO terms for kidney.

Hepato-renal toxicity of Myristica fragrans Houtt. (Myristicaceae) seed extracts in rats

ObjectivesMyristica fragrans is used in many parts of the world as a common spice and herbal medicine for managing a wide variety of ailments. The rich nutritional factors in M. fragrans seeds show potential application in food biofortification; however, the long-term safety of using a high dose of the seeds needs to be validated. This study seeks to investigate how oral administration of high doses of methanol (ME) and n-hexane (NHE) extracts of M. fragrans seed for one or two weeks affects the histology and serum markers of kidney and liver of rats. MethodsAdult male Swiss mice (6–7 weeks, 20–30 g) were used for acute toxicity study by standard methods, while male Wistar rats (6–8 weeks, 100–120 g) were used for sub-acute toxicity test. The sixty rats were distributed into five groups of 12 rats each: Group 1 received normal saline, groups 2 and 3 were orally treated with 500 and 1000 mg/kg b.w/day ME while groups 4 and 5 were fed 500 and 1000 mg/kg b.w/day NHE, respectively for 14 days. Six rats from each group were sacrificed on days 8 and 15 after 24 h of fasting. Markers of kidney and liver status of test and control animals were compared using one-way analysis of variance. ResultsThe presence of terpenoids, flavonoids, alkaloids, phenols, steroids, and tannins were detected in both extracts, although at varying levels. There was no obvious sign of toxicity nor mortality in acute toxicity test after 24 h of administration of extracts up to 5000 mg/kg b.w. However, there were significant (p < 0.5) elevations in urea, total bilirubin and creatinine concentrations, alkaline phosphatase, aspartate and alanine aminotransferases, and lactate dehydrogenase activities in rats fed extracts for seven or fourteen days relative to control. Furthermore, the n-hexane extract at 1000 mg/kg elicited some histological changes consistent with hepatotoxicity. ConclusionsAlthough the extracts were rich in some essential phytochemicals, this study demonstrated that long-term administration of high doses of the extracts elicits hepato-renal toxicities. Hence, consuming a large amount of the seed over a long duration is discouraged.

EFEKTIVITAS PLATELET-RICH PLASMA TERHADAP PERBAIKAN ORGAN GINJAL

Kidney Failure is a health condition that worsen the quality of life. In Acute Kidney Injury and Chronic Kidney Disease there is a damage not only in function but also in the structure of kidney. Platelet Rich Plasma is known to has a lot of benefits as a medical treatment. Platelet Rich Plasma is a plasma that rich in platelets which has the function of regenerating and repairing tissue structures, especially damaged kidneys. This study aimsTo determine the effectiveness of Platelet-Rich Plasma on the improvement of damaged kidneys. This paper uses a literature study or literature review by searching through Google Scholar or Pubmed using the keywords “Platelet-Rich Plasma”, “Acute Kidney Injury”, “Chronic Kidney Disease” for the last 5 years studies published between 2016 to 2021. Based on the literature search, there were 5 research articles related to the effectiveness of Platelet Rich Plasma on the improvement of damaged kidney, where all studies were tested on experimental animals. Based on the results of the literature study, it can be concluded that there is a relationship between the effectiveness of Platelet-Rich Plasma on the improvement of damaged kidneys in experimental animals.

Hemolymph Node – An Immunomorphlogical Organ: Modeling the Hemolymph Node by Allografting Renal Tissue in the Rat

There is no authoritative characterization of the attributes of the hemolymph node (HLN) since Gibbes’ first description in 1884. Early reports showed that HLN are found near the kidney in human and animals with the feature of numerous erythrocytes in sinuses. Subsequent studies mainly focused on anatomy and histology, such as the source, distribution, and quantity of erythrocytes in sinuses. Recent articles mentioned that the emergence of HLN was related to immunity, but there was no strong evidence to support this hypothesis. Therefore, it is still uncertain whether the HLN is an organ of anatomy, histology, or immunology. It has been found that the development of HLN could be elicited in the parathymic area by stimuli such as Escherichia coli, allogeneic breast cancer cells, and renal tissue that were injected/transplanted into the tail of rats in our pilot studies. In this study, the model of the HLN was established by transferring allogeneic renal tissue in the rat. Intrasinusoidal erythrocytes of the node were the component for producing a red macroscopic appearance, while macrophage-erythrocyte-lymphocyte rosettes were the major immunomorphological changes, reflecting the immune activity against the invasion of the allogeneic tissue within the node. Therefore, the HLN is an immunomorphological organ.

Effects of Phthalates on Animal Health

In daily life plastics are used widely due to their easy to use characteristics and low cost advantages. Some additives used in the contents of these plastics present more risk compared others. Especially, the plasticizers which soften and add elasticity to plastics form the highest risk. Phthalates, as plasticizers, are the most commonly used compounds used in sectors like food packaging, toys, make up products, medical instruments, textiles and construction materials. Phthalates, which used commonly in daily life, are not only chemically harmful; additionally they endanger the biologic system and also the health of all living creatures and organisms. These compounds are organic contaminants, they do not dissolve in water but dissolve in oil, they do not tie up with covalent bond to plastics. Thus they can easily spread to the environment through the multipath such as water, air and others. These phthalates which are inimical to health and nature, cause adverse effect on animals as well. One of the most commonly used phthalates di--(2 ethylhekzyl) DEHP causes liver, kidney and lung problems in animals when they are exposed to this compound, additionally it was found out that the reproduction systems of animals may be negatively affected, especially those that are exposed to phthalates during the postnatal period. Phthalates used in wide range of industrial scopes are among the chemicals materials that are carcinogenic, and they negatively affect hormonal metabolism. This paper discusses the negative effects of the highly toxic phthalates on animal health. Keywords: Phthalates, Animal health, Plasticizers DOI: 10.7176/JSTR/7-09-01

Surgical simulation of pediatric laparoscopic dismembered pyeloplasty: Reproducible high-fidelity animal-tissue model

To provide a high-fidelity, animal tissue-based model for the advanced surgical simulation of laparoscopic dismembered pyeloplasty in infants and children. A previously described animal tissue model using chicken crop was surgically modified and attached to piglet kidney specimens in order to provide organ model realistically resembling infant and children hydronephrosis for simulation of dismembered laparoscopic pyeloplasty. Dismembered pyeloplasty could then be carried out in a standard pelvi-trainer using a standard instrumentation as in a regular case. The model created could prove to be a high-fidelity, animal tissue model for the surgical simulation of dismembered pyeloplasty. The surgical modification of the used animal tissues of chicken crop and piglet kidney respectively used in this fusion model was able to provide a high grade of resembling a realistic organ situs for infant and pediatric pyeloplasty, respectively. The surgical procedure could be carried out as a simulation of a regular case while providing high-grade realistic anatomy, adequate sizes of a dilated renal pelvis and of the ureter, respectively. Biological as well as haptic conditions of the tissue were able to resemble human tissue in a high grade as well. Despite a live animal model has been described for dismembered pyeloplasty, its time-consuming creation and possible conflict concerning animal welfare cadaver models are more practicable for daily simulation. In literature so far animal-tissue models described range from folded chicken skin to a chicken crop model. While these types of models have its own advantages and disadvantages none of them provide adequate anatomical relations. By dissecting chicken crop and fixating it to a piglet's kidney this limitation could be overcome and furthermore will enable future modifications for a perfused model for laparoscopic dismembered pyeloplasty. The fusion of a previously described tissue model of chicken crop for simulation of pyeloplasty along with also previously used piglet kidneys for surgical simulation can provide a highly realistic model for surgical simulation of pediatric dismembered laparoscopic pyeloplasty. In addition, this model rules out the disadvantage of native animal kidney specimens which the lack of pathology of a dilated renal pelvis. Surgical modification is an established method to provide high-fidelity animal tissue models for surgical simulation and therefore training of complex procedures, respectively. For simulation purposes in pediatric laparoscopic urology, i.e., reconstructive procedures such as dismembered pyeloplasty this model appears to be promising in terms of providing realistic pathology in pediatric dimensions.

Detection of infection with hydatid cysts in abattoirs animals at Kirkuk governorate, Iraq

During the period from September 2020 to February 2021, the current study was conducted to determine the total prevalence of infection with hydatid cysts disease in the various organs (especially liver, lung, spleen, kidney, heart, and mesentery) of abattoirs animals (sheep, cattle, goats and buffaloes) in Kirkuk governorate and its suburbs. Visual examination and hand-feeling were used to detect and identify the site of infection with hydatid cysts, as well as a microscopic examination was used to determine the fertility of hydatid cysts.&#x0D; A total of 4122 abattoirs animals were examined, including: 1860 sheep, 1550 cattle, 680 goats and 32 buffaloes. The hydatid cysts was found in 133 animal samples (42 sheep, 83 cattle, 6 goats and 2 buffaloes), the total prevalence of infection was 2.25%, 5.35%, 0.88%, 6.25% in sheep, cattle, goats and buffaloes, respectively. The prevalence of infection in females of abattoirs animals was more than in males, which was 0.48%, 1.77% in sheep; 1.48%, 3.87% in cattle; 0.29%, 0.58% in goats, for male and female respectively. While, the prevalence of infection was 6.25% in females of buffaloes compared with their males which didn’t infected.&#x0D; The results showed that the liver is the most organ of the animal’s body to be infected with hydatid cyst, the prevalence of infection in the liver of males and females was 63.63%, 44.44% in sheep, 46.66%, 65.21% in cattle, 50.00%, 50.00% in goats and 0.00%, 50.00% in buffaloes, respectively.&#x0D; The infection with fertile hydatid cysts in sheep, especially in livers of females (80.95%) is higher compared with other infections of abattoirs animals, while it was noticed that the highest prevalence of sterile hydatid cysts in the lungs of females cattle (93.33%). In addition, the most cases of calcified hydatid cysts were observed in the lungs of females sheep (50.00%) and livers of females cattle (32.14%).

Francisella noatunensis subsp. orientalis outbreak in Nile tilapia juveniles cultivated in net cages in the Araguari river basin, Brazil

The aims at identifying and describing the occurrence ofanatomopathological and histopathological changes in Nile tilapia juveniles, naturally infected with Francisella noatunensis subsp. orientalis (Fno). The Nile tilapias of this study were cultivated in net cages in the region of the Araguari River basin, Minas Gerais, Brazil, and due to a mortality rate ranging from 40 to 60%, 64 fish samples were collected and sent for examination in the laboratory. At necropsy, granuloma-like nodules were observed in the spleen 59/64(92.2%), kidney 24/64 (37.5%), and liver 09/64 (14.1%). Fno was detected in 98% (49/50) of the samples by PCR. Upon analysis, astrong correlation was observed between external and internal lesions, since granulomatous lesions present in the spleen and kidney of the same animal simultaneously were also accompanied by skin ulcers, suggesting that the cutaneous lesion is related to the presence of Fno in tilapia and can be used as an indication for early diagnosis. Thus, the high prevalence of Fno observed in this research study allows characterizing an outbreak in the region. It is noteworthy that especially regarding the consumption of tilapia meat, although there are zoonotic species in the Francisella group, the zoonotic potential of Fno is not yet known and should be further studied.

The Toxic Effects of Low Molecular Weight Components of Cow Colostrums: The Short-Term and Long-Term Effects

Background: Low-molecular components of colostrum (LMWCC) have a pronounced biological activity. We investigated the effect of different doses of LMWCC (0.01, 0.1, 1 and 5 g/100 g of body weight) on the behavior, dynamics of growth, acute and chronic toxicity, as well as the relative weight of the liver, spleen and kidneys of the experimental animals. Methods: We used 100 3-month male rats in the experiment. All animals were divided into 5 groups of 20 animals in each group, LMWCC was administered per os, and the control group received sterile water. Results: LMWCC revealed no pirogenic effect in a wide diapason of doses (0,01-5 g/100 g of animal mass). Immediately after the LMWCC administration the short-time decrease in the motion activity was observed. The low doses of LMWCC induced diarrhea in 10-20 % of of animals, the super-large dose – in 75% of animals. The acute toxicity of LMWCC (death of 15 % of animals) was detected only in super-large dose of LMWCC and it was accompanied by pronounced diarrhea. LMWCC influenced the mass of liver, spleen and kidney. 60 days after LMWCC administration the mass of liver was restored to control weight, but the mass of spleen and kidney was not restored. Conclusion: LMWCCdo not have chronic toxicity and can be attributed to non-toxic compounds with a possible side effect - a violation of the digestive system.

The activation of nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling blunts cholestasis-induced liver and kidney injury.

Cholestasis is a severe clinical complication that severely damages the liver. Kidneys are also the most affected extrahepatic organs in cholestasis. The pivotal role of oxidative stress has been mentioned in the pathogenesis of cholestasis-induced organ injury. The activation of the nuclear factor-E2-related factor 2 (Nrf2) pathway is involved in response to oxidative stress. The current study was designed to evaluate the potential role of Nrf2 signaling activation in preventing bile acids-induced toxicity in the liver and kidney. Dimethyl fumarate was used as a robust activator of Nrf2 signaling. Rats underwent bile duct ligation surgery and were treated with dimethyl fumarate (10 and 40mg/kg). Severe oxidative stress was evident in the liver and kidney of cholestatic animals (P<0.05). On the other hand, the expression and activity of Nrf2 and downstream genes were time-dependently decreased (P<0.05). Moreover, significant mitochondrial depolarization, decreased ATP levels, and mitochondrial permeabilization were detected in bile duct-ligated rats (P<0.05). Histopathological alterations included liver necrosis, fibrosis, inflammation and kidney interstitial inflammation, and cast formation. It was found that dimethyl fumarate significantly decreased hepatic and renal injury in cholestatic animals (P<0.05). Based on these data, the activation of the cellular antioxidant response could serve as an efficient therapeutic option for managing cholestasis-induced organ injury.

The Impact of Functional and Structural Maturation of the Kidney on Susceptibility to Drug and Chemical Toxicity in Neonatal Rodents.

Drug responses are often unpredictable in juvenile animal toxicity studies; hence, optimizing dosages is challenging. Renal functional differences based on age of development will often result in vastly different toxicologic responses. Developmental changes in renal function can alter plasma clearance of compounds with extensive renal elimination. Absorption, distribution, metabolism, and excretion of drugs vary depending on animal age and kidney maturation. Toxicity can result in malformations or renal degeneration. Although renal morphologic development in humans generally occurs in utero, maximal levels of tubular secretion, acid-base equilibrium, concentrating ability, or glomerular filtration rate (GFR) are reached postnatally in humans and animals and subject to drug effects. Maturation of renal metabolism and transporters occurs postnatally and plays a critical role in detoxification and excretion. Maturation times must be considered when designing juvenile toxicity studies and may require cohorts of animals of specific ages to achieve optimal dosing schemes and toxicokinetics. In recent years, critical end points and windows of susceptibility have been established comparatively between species to better model pharmacokinetics and understand pediatric nephrotoxicity. There are examples of agents where toxicity is enhanced in neonates, others where it is diminished, and others where rat nephrotoxicity is expressed as juvenile toxicity, but in humans as gestational toxicity.

Bone marrow-derived mesenchymal stem cells transplantation ameliorates renal injury through anti-fibrotic and anti-inflammatory effects in chronic experimental renovascular disease

BackgroundProgressive renal fibrosis is an underlying pathological process of chronic kidney disease (CKD) evolution. This study aimed to evaluate the roles of bone-marrow-derived mesenchymal stem cells (MSC) in the remodeling of fibrotic kidney parenchyma in the two kidneys-one clip (2K1C) CKD animal model. MethodsWistar rats were allocated into three groups: Sham, 2K1C, and 2K1C þ MSC. MSCs (106) were transplanted into the renal subcapsular region two weeks after clipping the left renal artery. Six weeks after clipping, left kidney samples were analyzed using histological and western blotting techniques. ANOVA tests were performed and differences between groups were considered statistically significant if p < 0.05. ResultsClipped kidneys of 2K1C rats displayed renal fibrosis, with excessive collagen deposition, glomerulosclerosis and renal basement membrane disruption. Clipped kidneys of 2K1C þ MSC rats showed preserved Bowman's capsule and tubular basement membranes, medullary tubules morphological reconstitution and reduced collagen deposits. Expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were elevated, whereas tissue inhibitor of MMPs (TIMP)-1 and TIMP-2 levels were decreased in clipped kidneys of 2K1C rats. MSCs transplantation restored these expression levels. Moreover, MSCs suppressed macrophages and myofibroblasts accumulation, as well as TNF-a expression in clipped kidneys of 2K1C animals. MSCs transplantation significantly increased IL-10 expression. ConclusionsTransplanted MSCs orchestrate anti-fibrotic and anti-inflammatory events, which reverse renal fibrosis and promote renal morphological restoration. This study supports the notion that only one MSCs delivery into the renal subcapsular region represents a possible therapeutic strategy against renal fibrosis for CKD treatment.

The Effect of Venom of Egyptian Spitting Cobra Naja nubiae on Vascular Permeability of Hepatic and Renal Tissues

Background: Among venomous elapid snakes, cobras have the highest public awareness, as their venom represents a combination of proteins, peptides, and enzymes that have a range of biochemical and pharmacological roles and are also the main constitutes of biological activity and lethal toxicity. Objectives: The study aimed to evaluate the effect of the venom of Egyptian Spitting Cobra, Naja nubiae, on the vascular permeability based on the extravasation of the azo dye Evans blue (EB) into the tissues of the liver and kidneys of animals envenomed with low (¼ LD50; 0.32 mg/kg) and high (½ LD50; 0.65 mg/ kg) doses at three sampling times (30, 120, 360 min) post-injection of the venom. Methods: Fifty-four adult male Albino rats (8 weeks old and 180±2 0 g body weight) were divided into three main groups (n=6). In the control group, rats were subcutaneously (SC) injected with saline solution. Envenomed groups were SC injected, one group with 0.32 mg/kg and the other group with 0.65 mg/kg body weight of crude venom, respectively. Rats were I.V injected with EB dye 20 minutes before SC injection with saline solution as control animals and with Naja nubiae venom as treatment groups. Results: The results illustrated a high significant rate of EB extravasation to hepatic and renal tissues by the colorimetric determination of EB dye concentration. Conclusion: The venom of Naja nubiae can cause increased hepatic and renal vascular permeability which may explain the inflammatory effect induced by this venom.

Acute and Subchronic Toxicity Assessment of Proteins from Plumeria pudica Latex in Mice

Latex proteins extracted from Plumeria pudica (LPPp) have anti-inflammatory activity in different experimental models. Considering this relevant result, we evaluated the toxicological aspects of the treatment of mice with LPPp. Acute and subchronic toxicities were determined by daily intraperitoneal administration of 40 mg/kg of LPPp for 10 or 20 days, respectively, and were followed by behavioral, hematological, biochemical and histopathological evaluation. Results showed no significant changes in body weight and organs of animals treated with LPPp. Total and differential blood leukocyte counts of LPPp groups did not differ from controls. There was no significant difference in aspartate aminotransferase, alanine aminotransferase, creatinine and urea measurements for the group treated for 20 days. The level of glutathione in the kidney was significantly higher in animals treated with LPPp in the acute toxicity test, but no differences were observed for the subchronic evaluation. The concentration of malondialdehyde and myeloperoxidase activity in the organs did not differ from controls. Histopathological examination of kidney, spleen and liver tissue of animals treated with LPPp revealed normal structures or reversible alterations. Intraperitoneal LD50 of LPPp was higher than 2,000 mg/kg. The data obtained reveal that LPPp is nontoxic at 40 mg/kg.