Hyaline Droplets Research Articles

Impact of continuous Triazophos exposure on Labeo rohita: Physiological, biochemical, and histological alterations and IBRv2 index assessment

Pesticides are commonly used in agriculture and aquaculture. Triazophos, an organophosphate-based pesticide, is widely used in agriculture to control many insect pests. Due to its high photochemical stability and mode of action, Triazophos could persist in the aquatic ecosystem and cause toxic effects on non-target organisms. We have studied the potential toxic effects of Triazophos on L. rohita. Primarily, we determined the median lethal concentration (LC50) of Triazophos for 24 and 96 h. Next, we studied acute (96 h, LC50–96 h) toxicity. Then, we studied chronic (35 days, 1/10th LC50–24 h Treatment I: 0.609 mg/L, 1/5th LC50–96 h Treatment II: 1.044 mg/L) toxicity. We analyzed blood biomarkers such as hematology (Hb, Hct, RBC, WBC, MCV, MCH and MCHC), prolactin, cortisol, glucose and protein levels. Concurrently, we analyzed tissue biomarkers such as glycogen, GOT, GPT, LDH and histopathology. IBRv2 index assessment method was also to evaluate the Triazophos toxicity. Studied hematological, hormonal, biochemical and enzymological biomarkers were affected in Triazophos treated groups when compare to the control group. The changes in these biomarkers were statistically significant at the 0.05 alpha level. Triazophos exposed fish shown a severe degenerated primary and secondary lamellae, lamellar fusion, hypertrophy and telangiectasia in the gills. In the hepatic tissue, it caused moderate necrosis, blood congestion, distended sinusoids with minor vacuolation, prominent pyknotic nuclei, hypertrophy, cloudy swelling of cells, lipid accumulation and fibrotic lesions. In the renal tissue, Triazophos caused thickening of Bowman's capsule, hyaline droplets degeneration, irregular renal corpuscle, congestion, cellular swelling, degeneration of tubular epithelium, necrosis, shrunken glomerulus, vacuolated glomerulus, hypertrophy, exudate and edema. IBRv2 analysis suggested that tissue biomarkers are highly sensitive to Triazophos toxicity and prolonged exposure could cause serious health effects like acute toxicity in fish. Triazophos could cause multiorgan toxicity at studied concentrations.

Histopathology and micronuclei induction as pollution biomarkers in common carp, Cyprinus carpio from southern Iraq

This study aimed to assess the histopathological alterations and micronuclei induction in the gill, kidney and liver of common carp, Cyprinus carpio from Al-Huwaizah Marshes, Al-Hammar Marshes and Al-Sweap River. Thirty C. carpio were sampled at each locality using monofilament gillnets. Most prominent histopathological alterations recorded in the gill included formation venous sinus in primary lamellae, oedema, curling and distortion of primary lamellae fusion of secondary lamellae, hyperplasia of epithelial cells, necrosis, curling of secondary lamellae, severe dilation of lamellar capillaries, clavate lamellae formation at the tip of secondary lamellae, a proliferation of cartilage tissue in primary lamellae and lifting of the lamellar epithelium whereas congestion, fibrosis with proliferative inflammation, necrosis area, degenerated cells, vacuolar degeneration, vacuolation, nuclear pyknosis, hypertrophy of hepatocytes were reported in the liver. In the kidney, the most pronounced changes were necrosis of the hematopoietic tissue, hyaline droplet and activation of melanomacrophage centres. A higher prevalence of alterations was observed in the population from Al-Huwaizah Marshes, however, Al-Hammar population exhibited severe pathologies. Micronuclei frequency was significantly higher at Al-Huwaizah Marsh (p < 0.05) with low frequency being recorded at Al-Sweap River. This study attests to the effectiveness of histopathology and micronucleus induction as potential tools for discriminating the health of populations from different water bodies.

A 13-week subchronic toxicity study of linalool oxide in Crl:CD(SD) rats.

Linalool oxide is frequently used as a flavoring agent, however, data on its toxicity is limited. In this study, we performed a 13-week subchronic toxicity study of linalool oxide (furanoid) in male and female Crl:CD(SD) rats. Doses of 0, 80, 250, and 800 mg/kg body weight (bw) per day were orally administered by gavage, using corn oil as the vehicle. Abnormal gait in both sexes and decreased locomotor activity in males were observed in the 800 mg/kg group. Reduced body weight gain was noted in both sexes at 800 mg/kg and at 250 mg/kg in males. In the 800 mg/kg group, serum biochemistry showed increased γ-glutamyl transpeptidase and decreased glucose in both sexes, increased total protein in males, and increased total cholesterol and phospholipids in females, suggesting that linalool oxide may have adverse effects on the liver. Increased relative and/or absolute liver weights, centrilobular hepatocellular hypertrophy in both sexes, and periportal microvesicular fatty changes in females were observed in the 800 mg/kg group. Increased relative liver weights and decreased serum glucose levels were observed in the 250 mg/kg male and female groups, respectively. Increased serum magnesium levels and relative kidney weights were observed in both sexes in the 800 mg/kg group, suggesting possible adverse effects of linalool oxide. Although histopathology showed accumulation of hyaline droplets in the male kidneys, immunohistochemistry revealed α2u-globulin nephropathy, which was not considered toxicologically significant. These results indicate that the no-observed-adverse-effect level of linalool oxide was 80 mg/kg bw/day for both sexes.

Effect of photoperiod on serum biochemistry, electrolytic balance, acute phase response and histopathology of butter catfish, Ompok bimaculatus (Bloch, 1794).

The present study was executed to evaluate the effect of photoperiod on serum biochemical parameters (glucose, cortisol, ALT, AST and LDH), electrolytic balance (Sodium and potassium), acute phase response (CRP) and histopathology (liver, kidney and skin) of an endangered high valued catfish, Ompok bimaculatus. Catfish (21.00 ± 1.53cm and 30.00 ± 2.31g) from the acclimatized stock were randomly distributed to six 120 × 45 × 60 cm3 FRP tanks (n = 20 fish per tank) and exposed to 1500lx light intensity under different photoperiods [24:0 light: dark (L: D), 15L: 9D, 12L: 12D, 9L: 15D, 0L: 24D and a natural photoperiod (control)], and fed at a daily rate of 2% of bodyweight, twice a day for 60days. Serum glucose, cortisol and enzymes including aspartate transaminase (AST), lactate dehydrogenase (LDH), alanine transaminase (ALT), and acute phase reactant, such as C-reactive protein (CRP) increased significantly (P < 0.05) in continuous light (24L: 0D), continuous dark (0L: 24D) and short day (9L: 15D) photoperiods, whereas in 15L: 9D and 12L:12D photoperiods, those were in decreasing trend. Serum electrolytes, i.e. potassium level was elevated and sodium level was declined in 24L: 0D, 0L: 24D and 9L: 15D photoperiod groups. Moreover, significant histological alterations in the liver, kidney and skin tissue were also evidenced in the experimented catfish. Typical polygonal hepatocytes with normal blood vessels in liver and normal organization of kidney were seen in catfish of 15L: 9D group. Histological analysis of other groups displayed nuclear degeneration, karyorrhexis, karyolysis, melanomacrophages, nuclear hypertrophy, sinusoid dilation and vacuolar degeneration in liver and hyaline droplets accumulation, granular degeneration, fragmentation of glomerulus and focal necrosis of epithelial cells in kidney. Additionally, general structure of the skin was observed in control group as well as in 15L: 9D group. Contrarily, in 24L: 0D group increased number of mucous cells and vacuoles was observed in the skin of butter catfish. In 9L: 15D and 0L: 24D photoperiods, O. bimaculatus exhibited ruptured epithelial cells, enlarged alarm cells, fat cells, necrotic cells and vacuoles in the skin tissue. The present study depicted that 15L: 9D photoperiod can induce better health of catfish, O. bimaculatus, which, in turn, can help farmers to increase the production of this high valued catfish in future.

Toxicological effect of endocrine disrupting insecticide (deltamethrin) on enzymatical, haematological and histopathological changes in the freshwater iridescent shark, Pangasius hypothalamus

This study investigated the deltamethrin (DMN) induced harmful effects on Pangasius hypophthalmus using enzymatic activity, haematological, and histopathological changes. LC50 value was 0.021 mg/L at 96 h, and sublethal toxicity was tested for 45 days at two `concentrations (i.e., 1/5th and 1/10th of LC50). Haematological parameters and enzymatic activities significantly changed between DMN-exposed and control groups (p < 0.05). Histopathologically, both DMN doses induced liver hyperemia, hepatic cell rupture, necrosis, hypertrepheoid bile duct, shifting nuclei, vascular haemorrhage, and hepatocyte degeneration, while in gill, secondary lamellae destruction, a fusion of adjacent gill lamellae, hypertrophy, hyperplasia, adhesion, and fusion were noticed. Kidney developed melanomacrophages, increased periglomerular and peritubular space, vacuolation, decreased glomerulus, hyaline droplets in tubular cells, loss of tubular epithelium, distal convoluted segment hypertrophy, and granular layer in brain pyramid and Purkinje cell nucleus. But, limiting pesticide impacts on freshwater fish and their habitat requires a holistic, cradle-to-grave approach and toxicological studies.

A 90-day repeated oral dose toxicity study of 2-Butylbenzo[d]isothiazol-3(2H)-one in rats

2-Butylbenzo[d]isothiazol-3(2H)-one (BBIT, CAS No. 4299-07-4) is widely used as an industrial antiseptic and antifungal agent. To investigate its toxicological properties and determine the no-observed-adverse-effect level (NOAEL), a 90-day repeated oral toxicological study of BBIT was conducted in Crl:CD (SD) rats at doses of 0 (vehicle control, corn oil), 30, 90, or 270 mg/kg/day. There was no mortality or abnormal clinical signs related to treatment in any group. Slightly decreased body weight and food consumption were observed in the 270 mg/kg group in females. Increased urine volume and kidney weight, increased liver weight, and thickening of the forestomach mucosa in autopsy were observed in both sexes in the 270 mg/kg group. Histopathological examination revealed that hyperplasia of the squamous epithelium of the forestomach with parakeratosis and/or hyperkeratosis was observed in both sexes in all the BBIT-treated groups. Moreover, centrilobular hypertrophy of hepatocytes was observed in both sexes of the 270 mg/kg group. Similarly, increased depositions of eosinophilic bodies and/or hyaline droplets in the proximal tubules of the kidney were observed among the male in the 270 mg/kg group. Based on the forestomach changes, NOAEL was judged to be less than 30 mg/kg/day in both sexes under this study’s conditions.

Murine model for chronic rhinosinusitis: an interventional study

BackgroundChronic rhinosinusitis (CRS) is a complex inflammatory disease of the sinonasal tract. To understand this disease entity and develop targeted treatments, a reproducible animal model is paramount.Aims/objectivesTo optimize a murine model of eosinophilic CRS by establishing benchmark histological markers and validate its fidelity in evaluating intranasal treatments.Material and methodsForty-five Balb/c mice were included in the 7-week protocol. Experimental animals (n = 20) were induced a CRS disease state upon receiving intraperitoneal sensitization with ovalbumin (OVA), followed by intranasal OVA with Aspergillus oryzae protease. Analysis of complete blood count with differential, peripheral blood smear, and histological markers from the nasal cavity mucosa were performed. CRS mice were additionally treated with intranasal saline (n = 5) or mometasone (n = 10) and compared with control groups of untreated CRS (n = 5) and healthy (n = 5) mice after week 7.ResultsHistological analysis of experimental animal nasal mucosa revealed significantly higher levels of eosinophilic tissue infiltration/degranulation, hyaline droplets, Charcot–Leyden crystals, and respiratory epithelial thickness compared to healthy controls. Treatment with mometasone significantly reversed the histopathological changes observed in CRS mice.Conclusion and significanceThis murine model induced substantial local eosinophilic inflammation within sinonasal mucosa, that was reversible with mometasone. This model may be used to evaluate the efficacy of therapeutics designed to target CRS.

A 90-day dose toxicity study of 2-(2H-benzotriazol-2-yl)-6-dodecyl-4-methylphenol in rats

2-(2H-benzotriazol-2-yl)-6-dodecyl-4-methylphenol (BTMLP, CAS No. 125304-04-3) is widely used as a liquid ultraviolet absorber that prevents deterioration of synthetic resins and so on. To investigate its toxicological properties and determine the no-observed-adverse-effect level (NOAEL), a 90-day repeated oral toxicological study of BTMLP was conducted in Crl:CD (SD) rats at doses of 0 (vehicle control, corn oil), 100, 300, and 1000 mg/kg/day. There was no observed mortality or abnormal clinical signs related to the treatment of any group. Body weight and food consumption were not affected by BTMLP treatment. In males, significant prolongations of prothrombin time and activated partial thrombin time were observed in the BTMLP-treated groups. Histopathological examination revealed a slight increase of the eosinophilic bodies and hyaline droplets in the renal cortical tubules in the 1000 mg/kg group in males. As mentioned above, the toxic effect of the BTMLP was noted in the blood coagulation system and kidneys only in males. Based on these findings, the NOAEL was judged to be less than 100 mg/kg/day in males and 1000 mg/kg/day in females under this study’s condition.

Acute and Subchronic Oral Toxicity of Anthraquinone in Sprague Dawley Rats.

Objective: This study was conducted to evaluate the acute and subchronic toxicity of anthraquinone. An acute toxicity test was performed in female Sprague Dawley (SD) rats, and the oral median lethal dose (LD50) of anthraquinone was estimated to be >5000 mg/kg body weight (BW). In the subchronic study, groups of 10 male and 10 female rats were dosed with anthraquinone by gavage at 0, 1.36, 5.44, 21.76, and 174.08 mg/kg BW, 7 days/week for 90 days followed by a recovery period of 28 days. No appreciable toxic-related changes were observed in the 1.36 mg/kg BW group. When the animals received 5.44 mg/kg BW or more of anthraquinone, hyaline droplet accumulation in the renal tubules was observed in both the male and female rats, and anemia was observed in the females. When the anthraquinone dose reached 174.08 mg/kg BW, mild hepatocellular hypertrophy around the central vein of the hepatic lobule and hypothyroidism were observed in the female rats. During the recovery period, changes in clinical symptoms and parameters were considerably alleviated. Based on the results of this study, the no observed adverse effect level (NOAEL) for anthraquinone in rats was set at 1.36 mg/kg BW, and the lowest observed adverse effect level (LOAEL) was 5.44 mg/kg BW.

Repercussion of salinity on hematological parameters and tissue morphology of gill and kidney at early life of tilapia

This study was attempted to reveal the changes in three hematological parameters such as blood hemoglobin, number of white blood cells (WBCs) and number of red blood cells (RBCs) and one biochemical (e.g., glucose) parameter along with the changes in histomorphological structures of gills and kidney of Nile tilapia fry reared in saline water. Two experimental set up were used for two different age groups- 5 days-after-hatch (5DAH) and 15 days-after-hatch (15DAH) - to test a novel hypothesis: if a little difference in the age during the first exposure to saline water could produce any variation in the results. They were placed into 6 plastic drums having six different salinity levels: 0, 5, 10, 15, 20 and 25. After 60 days, at least 5 individuals were taken out from each drum to observe the above-hematological and histomorphological parameters. A two-way-ANOVA revealed that, except for hemoglobin, all the observed parameters have been affected the effect of age × salinity interaction (P<0.05). Between the two age groups, only the overall average glucose value and RBC count were significantly different. Among various salinity levels, only RBC and WBC counts differed significantly. Further, the mean glucose value, RBC counts and WBC count at different salinities differed significantly from the base mean value of each parameter. With regard to the histomorphological structure of the gills and kidney, various malformations were evident. Though hypertrophy, epithelial uplifting and epithelial necrosis were present as gill degenerations, hyperplasia was prevalent across almost all salinity levels. On the other hand, glomerular necrosis, pyknotic nucleus, hyaline droplets degeneration, shrinking of the glomeruli, etc. were observed in kidney structures. By assisting to understand the effects of salinity stress, all these data on tilapia fry will help to determine the prospects and scope of culturing the species in high-salinity water.

The effects of dietary exposure to Magnéli phase titanium suboxide and titanium dioxide on rainbow trout (Oncorhynchus mykiss)

Magnéli phase titanium suboxides (Magnéli TiOx) are promising, novel materials with superior properties compared to TiO2, they are substoichiometric titanium oxides with the chemical formula TinO2n-1 (where n ≥ 1). In this study, for the first time, subchronic effects of dietary intake of Magnéli TiOx were evaluated and compared with TiO2 particles of similar size, in concentrations 0.1% and 0.01% of feed. The experiment consisted of 38 d of an exposition period and 14 d of a depuration period. Minor effects on plasma biochemical profile and morphological parameters were recorded. A reduced count of leukocytes was found in the blood of both Magnéli TiOx and TiO2 exposed fish, suggesting immunotoxic effects. Erythrocytosis was specific for Magnéli TiOx. Indices of oxidative stress, namely increased lipid peroxidation in liver, increased activity of superoxide dismutase in liver, kidney and gills and glutathione S-transferase (GST) in gills, as well as decreased activity of ceruloplasmin and GST in liver were found predominantly in fish exposed to TiO2. Histopathological examination revealed increased lipid-like vacuolation in the liver, the presence of hyaline droplets in renal tubules and multiplication of mucous glands in the epidermis in both tested substances and intestine damage in TiO2 groups.Overall, in Magnéli TiOx exposed groups, fewer adverse effects compared to TiO2 expositions were recorded. Their wider practical implementation in place of TiO2 is therefore beneficial.

Pathological aspects of experimental infection of Lactococcus garvieae in European Sea Bass (Dicentrarchus labrax L.): Clinical, hematological, and histopathological parameters

This study, it was aimed to examine the clinical, hematological, and histopathological aspects of lactococcosis induced in European sea bass (Dicentrarchus labrax), which was experimentally infected with Lactococcus garvieae. For this purpose, the infection was induced intraperitoneally with L. garvieae strain (108 CFU/mL), and blood samples were collected from the infected fish on different days (6, 18, 26, 31, 36, 44, and 48th) of infection. The morphological structures, erythrocyte and leukocyte count, hematocrit value, sedimentation rate, and coagulation time of the blood cells in the collected samples were calculated. As a result of the infection, while there was a decrease in erythrocyte count, hematocrit value, and coagulation rate, in addition to changes in the morphological structure of blood cells, it was determined that there was a significant increase in the leukocyte count and sedimentation rate. Furthermore, histopathological examination was also performed in the organs of infected fish such as the brain, liver, spleen, kidney, heart, gill, and intestine. Histopathologically, in the infected sea bass, while hemorrhage, diffuse necrosis, and hyaline droplets were detected in the granular brain tissue, hyperemia and hemorrhage were noted in the liver and spleen, and widespread necrosis in the hematopoietic tissue of the kidney, in the gills intensive hyperplasia, an increase in the goblet cell were detected. Although there are studies on lactococcosis in various marine fish species around the world, the infection of L. garvieae in farmed sea bass and various parameters and pathological aspects were investigated in detail for the first time in this study. L. garvieae was determined to have clinical significance for European sea bass with a high economic value.

Histopathological alterations in Van fish (Alburnus tarichi Güldenstädt, 1814) exposed to tebuconazole

ABSTRACT Tebuconazole (TEB) is one of the most commonly used fungicides in the Lake Van Basin in the Eastern Anatolia Region, Turkey, which is one of the largest alkaline lakes in the world. In this study, the effects of TEB on the Van fish, the only vertebrate species living in Lake Van were investigated. The TEB was administered at a dose of 2.5 mg/L to the Van fish, which were examined histologically via the gill, liver, and kidney tissues after 24, 48, 72 and 96 h of exposure to TEB. Normal histological structure was observed in the gill, liver, and kidney tissues in the control group. Epithelial hyperplasia, epithelial necrosis, epithelial lifting, lamellar fusion, and an increase in mucus cell counts were observed in the gill tissues of the fish exposed to TEB. Dilatation and congestion of the sinusoids, melano-macrophages aggregation, and, focal necrosis were detected in the liver tissues of the fish exposed to TEB. Bleeding in the kidney tissues, hyaline droplet degeneration, contraction of the glomerulus and enlargement of the space within the Bowman’s capsule were observed. The findings of the present study indicated that sublethal concentrations of TEB result in histopathologic changes in the gill, liver, and kidney.

A 90-day subchronic toxicity study of Myrrh in F344 rats

Myrrh is a flavoring agent and food additive. Here, we performed a subchronic toxicity study of Myrrh in male and female F344 rats by feeding at 5,000, 15,000 and 50,000 ppm for 90 days. No deaths or clinical signs were observed. Suppression of body weight gain was observed from the early phase of administration in both males and females in the 50,000 ppm group. Because there were no obvious changes in food intake in any of the Myrrh groups compared with the control group, suppression of body weight gain was considered an adverse effect of Myrrh. Hematology and serum biochemistry parameters with significant changes observed in the Myrrh groups were considered to have no toxicological significance. We observed a significant increase in relative kidney weight in male rats treated with 50,000 ppm Myrrh; this effect was considered to be related to the appearance of hyaline droplets in the epithelium of the proximal tubules histopathologically observed in this group. Immunohistochemical staining with anti-α2u-globulin antibodies suggested that these hyaline droplets were caused by factors other than α2u-globulin deposition. Thus, the no-observed-adverse-effect level of Myrrh was determined to be 15,000 ppm (males: 0.85 g/kg/day, females: 0.95 g/kg/day).

Immuno-pathological changes in Indian catfish Clarias magur (Hamilton, 1822) upon experimental challenge with Aeromonas hydropila

Motile Aeromonas septicaemia (MAS), caused by Aeromonas hydrophila, is one of the most significant problem among the bacterial diseases responsible for causing mortality in catfishes. The objective this study was to understand the modulation of innate immune parameters and histopathological alteration in Indian catfish Clarias magur (Hamilton, 1822), following intraperitoneal injection with A. hydrophila. At 3 to 8 h post-infection (hpi), respiratory burst activity, myeloperoxidase, protease, total anti-protease and α2 macroglobulin increased significantly (p<0.05) indicating immune response of host against pathogen invasion at an early stage of infection. The total protein, albumin, albumin/globulin ratio and bactericidal activity were significantly decreased indicating the response of pathogen to suppress host immune response to establish infection. Serum bactericidal activity, bacterial agglutination titre and lysozyme activity increased significantly at 24 hpi. Histopathological examination of infected fish revealed the accumulation of melanomacrophage centres, congestion, hepatocyte degeneration and vacuolated hepatocytes of liver; hyaline droplet accumulation, lymphocytes infiltration and diffuse necrosis of renal tubule in kidney; unilateral fusion of secondary gill lamellae, leukocytic infiltration as well as dilated central venous sinus in gills. Knowledge regarding the immune response in magur could be useful for developing strategies for improving disease resistance against A. hydrophila infection. Keywords: Aeromonas hydrophila, Histopathological alterations, Indian catfish, Innate immune parameters, Intraperitoneal challenge

Renal Alterations Induced by Chronic Exposure to Therapeutic Doses of Antihypercholestremic Atorvastatin.

Atorvastatin (ATOR) is widely used for the treatment and prevention of hypercholesterolemia and various diseases, such as cardiovascular complications, with little data about the histopathological and ultrastructural renal alterations that might be induced by this drug. The present study was undertaken to investigate the potential toxicity of therapeutic doses of atorvastatin on the microanatomy and ultrastructure of renal tissues from Wistar albino rats. Adult male Wistar albino rats received an oral daily dose of 5 mg/kg bodyweight for 90 consecutive days. Biopsies from both kidneys of each study rat were taken for histopathological and ultrastructural examination. ATOR-treated rats exhibited glomerular, tubular, and interstitial histological alterations, including degeneration, necrosis, hyaline droplets, edema, cortical hemorrhages, mesangial hypercellularity, and blood capillary dilation and congestion. In addition, ATOR exposure increased the activity of glucose-6-phosphate dehydrogenase and alkaline phosphatase with a concurrent reduction in proteins and neutral mucosubstances content of the glomeruli and renal cells. Moreover, ATOR-treated animals demonstrated glomerular ultrastructural alterations, consisting mainly of capillary tuft dilatation, glomerular basement membrane thickening, and mesangial cell proliferation. The renal cells of the proximal tubules demonstrated damaged mitochondria, degenerative cellular changes, endoplasmic reticulum dilatation, lysosomal and autophagosome activation, nuclear alteration, myelin figure formation, and microvilli disorganization. The findings of the present work may indicate that ATOR can induce renal histological, histochemical, and ultrastructural alterations that may affect kidney and other vital organ functions.

Comparison of sulfolane effects in Sprague Dawley rats, B6C3F1/N mice, and Hartley guinea pigs after 28 days of exposure via oral gavage.

Sulfolane is a solvent used in industrial refining with identified environmental exposure in drinking water. Due to potential large species differences, the National Toxicology Program (NTP) conducted 28-day toxicity studies in male and female Hsd:Sprague Dawley® SD® rats, B6C3F1/N mice, and Hartley guinea pigs. A wide dose range of 0, 1, 10, 30, 100, 300, and 800 mg/kg was administered via gavage. Histopathology, clinical pathology, and organ weights were evaluated after 28 days of exposure. In addition, plasma concentrations of sulfolane were evaluated 2 and 24 h after the last dose. Increased mortality was observed in the highest dose group of guinea pigs and mice while decreased body weight was observed in rats compared to controls. Histopathological lesions were observed in the kidney (male rat), stomach (male mice), esophagus (male and female guinea pigs), and nose (male guinea pigs). Plasma concentrations were generally higher in rats and guinea pigs compared to mice with evidence of saturated clearance at higher doses. Male rats appear to be the most sensitive with hyaline droplet accumulation occurring at all doses, although the human relevance of this finding is questionable.

Protective effect of Nannochloropsis Oculata against mercuric-induced histopathological alterations in the kidney of Nile tilapia

Objective: The present study was designed to evaluate the toxic effect of sublethal concentration of mercuric chloride (0.3 mg/L HgCl2) on histopathological lesions in the kidney of Nile tilapia (O. niloticus) and the protective effect of microalgae, Nannochloropsis oculata (N. oculata) against the induced tissue alterations for 3 weeks. Design: Randomized controlled study Animals: Nile tilapia Procedures: Fish were randomly assigned to 4 groups, group1: control (basal diet), group 2 (Hg/ exposed to HgCl2 at a dose of 0.3 mg/L (1/4 of LC50), and fed basal diet), group 3: (Hg+N5, similar to group2, but fed diet supplemented with N. oculata 5% and group 4 (Hg+N10, similar to group2, but fed diet supplemented with N. oculata 10 %. Two fish from each aquarium tank (6 fish/group) were sampled at weeks 1, 2, and 3 of the experiment. The posterior kidney was dried out in a graded ethanol series and then embedded in paraffin. Each block of tissue was cut into serial sections (5 μm thick) and stained with hematoxylin and eosin (H&amp;E). Results: Histopathological alterations were induced following mercuric exposure in a time-dependent manner. The kidney showed congestion, hemosiderosis, and hemorrhage with vacuolated tubular epithelium, hyaline droplet degeneration, and necrosis of the tubular epithelium. Supplementation with N. oculata, particularly at 10 %, succeeded in alleviating the histopathological induced lesions in the kidney. Conclusion and clinical relevance: Our findings demonstrate that HgCl2 has nephrotoxic properties that led to severe histopathological alterations in the kidney of Nile tilapia, while dietary supplementation with N. oculata was able to alleviate the induced kidney alterations.

Protective effect of Nannochloropsis Oculata against mercuric-induced histopathological alterations in the kidney of Nile tilapia.

Objective: The present study was designed to evaluate the toxic effect of sublethal concentration of mercuric chloride (0.3 mg/L HgCl2) on histopathological lesions in the kidney of Nile tilapia (O. niloticus) and the protective effect of microalgae, Nannochloropsis oculata (N. oculata) against the induced tissue alterations for 3 weeks. Design: Randomized controlled study Animals: Nile tilapia Procedures: Fish were randomly assigned to 4 groups, group1: control (basal diet), group 2 (Hg/ exposed to HgCl2 at a dose of 0.3 mg/L (1/4 of LC50), and fed basal diet), group 3: (Hg+N5, similar to group2, but fed diet supplemented with N. oculata 5% and group 4 (Hg+N10, similar to group2, but fed diet supplemented with N. oculata 10 %. Two fish from each aquarium tank (6 fish/group) were sampled at weeks 1, 2, and 3 of the experiment. The posterior kidney was dried out in a graded ethanol series and then embedded in paraffin. Each block of tissue was cut into serial sections (5 μm thick) and stained with hematoxylin and eosin (H&E). Results: Histopathological alterations were induced following mercuric exposure in a time-dependent manner. The kidney showed congestion, hemosiderosis, and hemorrhage with vacuolated tubular epithelium, hyaline droplet degeneration, and necrosis of the tubular epithelium. Supplementation with N. oculata, particularly at 10 %, succeeded in alleviating the histopathological induced lesions in the kidney. Conclusion and clinical relevance: Our findings demonstrate thatHgCl2 has nephrotoxic properties that led to severe histopathological alterations in the kidney of Nile tilapia, while dietary supplementation with N. oculata was able to alleviate the induced kidney alterations.

Four-week repeated dose oral toxicity study of KDS2010, a novel selective monoamine oxidase B inhibitor, in Sprague Dawley rats

Repeated dose oral toxicity and toxicokinetic of KDS2010, a new drug for Parkinson's disease, was investigated after 4-week repeated oral administration at 30, 50, 75, or 100 mg/kg/day in rats. Body weight and body weight gain decreased in rats of both sexes in the 75 and 100 mg/kg groups, and food consumption was reduced in male rats of the 75 and 100 mg/kg male groups. Histological alterations were observed in the kidney (urothelial hyperplasia, inflammatory cell infiltration in the renal pelvis, tubular vacuolation/degeneration, basophilic tubules, and hyaline droplets in the proximal tubules) of the 75 and 100 mg/kg male groups and the 50 and 100 mg/kg female groups. The 75 and 100 mg/kg male groups showed adverse effect in the testes (degeneration/exfoliation of germ cells, seminiferous tubules atrophy) and epididymis (cellular debris, oligospermia). These changes were partially recovered after a 2-week recovery period. However, basophilic tubules and hyaline droplets in the proximal tubules in the kidney and germ cell degeneration/exfoliation in the testis were not recovered. In toxicokinetics study, systemic exposure to KDS2010 increased proportionally in both sexes by in a dose -dependent manner. In addition, repeated administration for 4 weeks led to increased tendency of systemic exposure in both sexes compared with that in Day 1. In conclusion, KDS2010 was shown to target the kidney and testis with a no-observed-adverse-effect level of 50 and 30 mg/kg/day for males and females, respectively.