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Jul 2020 DOI 10.14302/issn.2576-6694.jbbs-20-3450
M. Mahmoud MagdyCorresponding author
Faculty of Science, Ain Shams University, Cairo Egypt.
Background Hyperphenylalaninemia (HPA) combined with neurological signs due to impaired catecholamine, dopamine and serotonin synthesis. Symptoms may appears in first week of life but most seen in age of 4 months. Atypical PKU disease caused mainly by deficiency in 6-pyruvoyltetrahydropterin synthase (PTPS) involved in synthesis of BH4. Clinical symptoms may include poor sucking, impaired tone, ataxia, and seizures. The purpose of this study was to analyze the genotype-phenotype relation among BH4 deficient patients because of PTPS mutations in different state of Egypt. Methods Suspected PKU patients loaded with phenylalanine/Kuvan, and the level of phe and phe/tyrosine ratio determined using tandem mass spectrometry by dried blood spots. Blood samples of 13 unrelated Egyptian patients were collected for total RNA extraction, amplification of PTPS gene by PCR followed with sequencing by Sanger method and finally mutations were recorded for genetic analysis. Results The mean value of phe in 13 patients decreased after loaded of phenylalanine from 482.5μmol/L to 270.63 μmol/L as well as phe/tyrosine ratio was decreased from 13.4 to 6.36 after 24hour of treatment with Kuvan. Sanger sequencing of PTPS gene of those patient showed 21 SNPs and Indels mutations. The most repeated mutation is a novel 23 base pair homozygous deletion in 12/13; c.200C>T in four patients, a novel c.86A>T in two patients and three different mutations located once in three different patients (novel c.22C>T; novel c.273G>A and 405T>C) among patients. On amino acid predicted sequences 4 different types of mutations on protein level were presented, 1 deletion mutation in seven amino acid and 3 different missense mutations in addition to 2 silent mutations among 13 patients. Conclusion Patients were the first case of clinical diagnosis as hyperphenylalaninemia (HPA) undergoing genetic diagnosis for PTPS deficiency in Egypt. The sever HPA patients with severe nervous system damage mainly accompanied with deletion mutations and should pay more attention to the BH4 deficiency. While mild HPA is associated with base substitution mutations with mainly transition mutations (7/9; 78%). Next-generation sequencing technique can increase the mutation detection rate when the hereditary diseases are highly suspected in clinic.
Mar 2020 DOI 10.14302/issn.2637-6075.jpae-20-3198
C. Izah SylvesterCorresponding author
Department of Biology, Bayelsa Medical University, Yenagoa, Bayelsa State, Nigeria.
Aminoforce containing 720g/l of 2,4-dimethylamine salt induced changes on some enzymes and electrolytes in the male Oryclotagus cuniculus (New Zealand rabbit) were assayed. The organisms were exposed to varying sub-lethal concentrations of the toxicant (720g/l). The concentrations were prepared by pipetting 0.4mls, 0.8mls and 0.12mls making it up to 1.5L clean water in a metal container to make 2.0 mgl-1, 4.0 mgl-1 and 6.0 mgl-1. Aspartate amino transferase (AST), Alanine amino transferase (ALT) and Acid phosphatase (ACP) were assayed in the liver and blood. Results showed that aspartate amino transferase values in the liver and blood were significant (p<0.05) across the concentration of the toxicants. Aspartate amino transferase increased as the concentration of the toxicant increased in the liver, and decreased as the toxicant concentration increased in the blood. Alanine amino transferase in the blood and liver were akin to AST while ACP values increased in the blood and decreased in the liver as the concentration of the toxicant increased. Electrolytes (Sodium (Na+), potassium (K+) and magnesium (Mg2+) ions) showed statistical deviation across the various concentration of the toxicants. Chloride ion values stabilized in the experimental group being not significantly different (p>0.05) across the various concentration of the toxicants. From the study, AST, ALT and ACP are suitable biomarkers for showing sub-lethal effect of aminoforce on Oryclotagus cuniculus. The effects recorded clearly unveiled the potential effect of this xenobiotics on Oryclotagus cuniculus. Therefore, exposure of Oryclotagus cuniculus to this toxicant will affect the organism’s physiological responses and over prolong period of time it could lead to death. Additionally, via food chain man may be affected. The use of this toxicant close to rabbittory should be done with utmost caution.
Oct 2019 DOI 10.14302/issn.2637-6075.jpae-19-3022
Chibueze Izah SylvesterCorresponding author
Department of Biological Sciences, Bayelsa Medical University, Yenagoa, Bayelsa State, Nigeria.
This study assessed the effect of aluminum phosphide on transferases in liver and muscle of Parophiocephalus obscurus (with mean weight of 42.20±1.5 gSD and mean length of 16.50± cmSD, respectively). The fish were obtained from a private fish farm in Yenagoa Metropolis, Nigeria, and the fish was allowed acclimatized to laboratory condition for 7 days, and then exposed to sublethal concentrations (0.00mg/L, 4.20mg/L, 6.30mg/L and 8.40mg/L) of aluminum phosphide for 14 days. Renewal bioassay was adopted in this study. At the end of the experimental period, the fish was dissected and the muscle and liver were collected, processed and analyzed for alanine aminotransferase and aspartate aminotransferase using colorimetric method. Results of the phosphatase at 0.00mg/L, 4.20mg/L, 6.30mg/L and 8.40mg/L were 94.50±6.44µ/L, 134.47±15.27 µ/L, 106.47±9.21 µ/L and 31.00±3.46 µ/L, respectively (liver), 107.50±9.24, 92.00±6.93 µ/L, 116.50±8.95 µ/L and 146.33±9.33 µ/L respectively (muscle) for aspartate aminotransferase; and 40.00±1.15µ/L, 26.50±3.18µ/L, 14.50±2.02µ/L and 9.80±1.44 µ/L, respectively (liver) and 17.00±1.75µ/L, 8.50±0.87µ/L, 21.00±2.89µ/L and 5.50±0.87 µ/L, respectively (muscle) for alanine aminotransferase. Statistically, there were significant variations (p<0.05) among the various concentration in the transferances. In addition, at some concentration, there was significant variations (p<0.05) between the level of the transferases in the muscle and liver. The significant alteration observed in the various concentrations is an indication that aluminum phosphide is lethal to fish. Therefore, caution should be exercise during the use of aluminum phosphide near biological system.
Oct 2018 DOI 10.14302/issn.2328-0182.japst-18-2341
Nyunaї NyembCorresponding author
The present investigation was carried out to evaluate the safety of a stem bark aqueous extract of Harunganamadagascariensis Lam. (Hypericaceae) by determining its potential toxicity after acute and subacute administration in rodents. Acute toxicity tests were carried out in mice and the behavior, death and median lethal dose (LD50) were estimated. Subacute toxicity (28 days) studies were conducted in rats with oral daily doses of 200, 400 and 600 mg/kg. Parameters observed at the end of the subacute tests included changes in body and vital organ weights, mortality, hematological, biochemical, hepatic and kidney effects. Harunganamadagascariensisextract did not produce any visible toxicity or mortality with oral doses up to 2000 mg/kg within 14 days of single treatment, leading to the conclusion that the LD50 is greater than 2000 mg/kg. In the subacute toxicity tests, neither mortality nor visible signs of lethality was seen in rats. No significant change in the weight of the kidney, liver, heart, lungs spleen, pancreas and testicles was observed. Alanine transaminase (ALT) increased significantly in males at 400 and 600 mg/kg, whereas Aspartate transaminase (AST) decreased at 600 mg/kg in female rats. HDL Cholesterol was reduced at 600 mg/kg in female rats. There was a significant increase in urea concentration in female rats at 400 mg/kg. A significant decrease, both in platelet volume distribution (PVD) at 400 mg/kg in male rats and in red cell volume distribution (RDW) at 200 mg/kg were recorded in female rats respectively, but with no changes in other hematologic parameters. Histological study shows normal structure of liver, kidneys and heart of control and treated rats. Results indicate that oral doses of aqueous stem bark of Harunganamadagascariensis are relatively safe in rats; however, assessment of hepatobiliary function should be done during chronic use in humans.
Dec 2017 DOI 10.14302/issn.2641-7669.ject-17-1789
M.E.Abdel-Salam OmarCorresponding author
Departments of Toxicology and Narcotics
We aimed to study the effect of buspirone, an anxiolytic drug and 5-HT1A agonist on liver injury induced by carbon tetrachloride (CCl4) in rats. Rats were orally treated with CCl4 (2.8 mL/kg in olive oil) along with buspirone at 10, 20 or 30 mg/kg once daily starting with CCl4 and for one week thereafter. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities were determined in the serum. Markers of oxidative stress: lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH), nitric oxide (nitrite/nitrate) levels were measured in the liver. Moreover, paraoxonase 1 activity was determined in the liver and serum. The administration of CCl4 led to significant increases in serum ALT, AST, and ALP activities. Results showed that there were significantly increased hepatic MDA, nitrite and decreased GSH levels. PON1 activity decreased both in the liver and serum, respectively. The immunohistochemical investigations using anti-caspase-3 antibody revealed that CCl4 caused apoptosis to many hepatocytes. DNA studies showed that CCl4 caused hypoploidy in hepatocytes. Rats treated with 20-30 mg/kg buspirone showed significant decrease in serum ALT and AST by 19.5-34.3% and 24.2-31.4%, respectively. Serum ALP decreased by 21.7% after 30 mg/kg buspirone. In the liver, the higher dose of the drug resulted in decreased MDA (by 15.8%), decreased nitric oxide (17.4%) and increased GSH (by 20.1%). Significantly increased serum PON1 activity by 43.9-53.5% was observed after treatment with 20-30 mg/kg buspirone. On histopathologic examination of liver sections, there was mild protective effect for the drug at 30 mg/kg. Sections stained with anti- caspase- 3 confirmed the results obtained from histopathological examination. Moreover, buspirone given at 30 mg/kg resulted in an increase in % of cells containing normal values of DNA. These results indicate that buspirone decreases liver oxidative stress and exerts protective effect against CCl4- toxicity. The study thus indicates more beneficial effects of buspirone as an anxiolytic drug and that the drug could be used safely in patients with liver disease.
Aug 2017 DOI 10.14302/issn.2471-2140.jaa-17-1541
Yu ZhiCorresponding author
College of Horticulture and Forestry Science, Huazhong Agricultural University, Key Laboratory of Horticultural Plant Biology, Ministry of Education, No. 1 Shizishan Street, Hongshan District, Wuhan City, Hubei Province, China 430070
In the present study, we investigated the chemical compositions, in vitro antioxidant and in vivo hepatoprotective activities of two tea polysaccharides (TPS), which were extracted from two different tea cultivars, Yingshuang (Camellia Senesis, T01) and Yunnan Dayezhong (Camellia Senesis, T09). Compared with T09-TPS, T01-TPS had lower contents of neutral sugar, protein, uronic acid and polyphenol. However, T01-TPS showed stronger scavenging abilities for transient free radicals of hydroxyl radical and superoxide anion radicals and lipid peroxidation inhibition effect, but weaker scavenging ability for stable free radical of DPPH. For hepatoprotective activity in vivo, the results demonstrated that both T01-TPS and T09-TPS could significantly prevent the increase of serum alanine aminotransferase and, aspartate aminotransferase levels, decrease the liver index, reduce the formation of malonydialdehyde and enhance the activities of superoxide dismutase, glutathione peroxidase and peroxidase in carbon tetrachloride-induced liver injury mice. These results suggest that T01-TPS and T09-TPS have potent antioxidant and hepatoprotective activities.