Hepatoprotective effects of walnut oil and Caralluma tuberculata against paracetamol in experimentally induced liver toxicity in mice.

Walnut Oil and Caralluma are edible and form part of the traditional medicine system in many countries. These are frequently used in traditional medicine as remedies to relieve a wide range of illnesses and health problems. Walnut Oil and Caralluma species have demonstrated anti-inflammatory, anti-nociceptive, antidiabetics, hepatoprotective, gastric mucosa protecting, antimalarial, antioxidant, anti-trypanosomal, appetite suppressant and cytotoxic activities. The current study was planned to study the impacts of 21 days' oral administration of walnut oil and methanolic extract of Caralluma tuberculata on the levels of some liver-associated parameters and hematological parameters in paracetamol intoxicated mice. It was observed that paracetamol intoxication resulted in a considerable rise in serum ALT, cholesterol, triglycerides, Creatinine, and urea levels while a decrease in HDL level in comparison to mice normal control group (P<0.05). Serum ALT, cholesterol, triglycerides, creatinine, and urea levels of mice that were administered with walnut oil and methanolic extract of C. tuberculata at the doses of (1 ml/kg, 2 ml/kg and 3 ml/kg body weight) were significantly lower when compared to toxic control mice group (P<0.05), While HDL level was significantly increased. The significant reduction had also been observed in the levels of serum parameters of mice group, which received standard hepato-protective drug i.e., vitamin C, at the dose of 8 mg/kg body weight (P<0.05). Based on these results, it was evident that liver toxicity caused by the paracetamol administration has recovered toward the normal range by the walnut oil and C. tuberculata extract. Therefore, the present study revealed that (walnut oil and C. tuberculata) exhibit hepatoprotective activities in paracetamol intoxicated mice.

Molecular Diagnosis and Identification of Genetic Variants Underlying Distal Renal Tubular Acidosis in Pakistani Patients Using Whole Exome Sequencing.

Introduction: Primary distal renal tubular acidosis (dRTA) is a rare genetic disorder characterized by an impaired urinary acidification process in distal nephrons that results in the production of alkaline urine. Loss of function variants in any of the three genes, ATP6V0A4, ATP6V1B1, or SLC4A1, which all play a role in normal acidification of urine by kidneys, may lead to dRTA. Objective: This study was designed to identify genetic variants underlying dRTA in Pakistani patients using whole exome sequencing, followed by confirmatory Sanger sequencing. Materials and Methods: Patients were identified following presentation with characteristic clinical features of dRTA including vomiting, dehydration, and highly alkaline urine with metabolic acidosis during the first few days of life. Whole exome sequencing and Sanger sequencing were employed for genetic analyses of the patients. In silico analyses of the identified variants were performed using web-based bioinfomatics programs. Results: Through whole exome sequencing, we identified two splice site variants (c.2257 + 1G>A and c.722 + 5G>A) in the ATP6V0A4 gene that likely underly the disease phenotype in the two families. Multiple in silico tools predicted these variants to affect the respective splice sites supporting their likely role in pathogenesis. Conclusion: The study extends the spectrum of ATP6V0A4 variants associated with dRTA and should benefit the genetic counseling and prenatal diagnosis of the affected families.

Whole exome sequencing identified three ABCC6 variants in two Pakistani families with pseudoxanthoma elasticum phenotype.

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder of ectopic mineralization and fragmentation of elastic fibers in skin, eyes, cardiovascular and digestive system. PXE is caused by sequence variants in ABCC6, which encodes multidrug resistance-associated protein 6 (MRP6, also known as the ABCC6 protein). MRP6 is an important regulator of inorganic plasma pyrophosphate that acts as an inhibitor of ectopic mineralization observed in PXE patients with low inorganic plasma pyrophosphate levels. The current study was designed to investigate underlying genetic defect in two unrelated Pakistani families affected with PXE. Whole exome sequencing followed by Sanger sequencing was performed to identify causative variants. A novel homozygous frameshift variant (c.1799_1805dupGTCTGGT) was identified in one family and two previously reported missense variants (c.2294G > A and c.2974G > A) in compound heterozygous form in the other family. We identified ABCC6 variants that are likely cause of the PXE disease in the tested families. Genetic analysis of these families could be useful for pre-symptomatic diagnosis and genetic counselling of the affected families.