The standardized extract of Centella asiatica L. Urb attenuates the convulsant effect induced by lithium/pilocarpine without affecting biochemical and haematological parameters in rats.

BACKGROUND: Status epilepticus (SE) is a type of epileptic activity characterized by a failure of the inhibitory mechanisms that limit seizures, which are mainly regulated by the GABAergic system. This imbalance increases glutamatergic neurotransmission and consequently produces epileptic activity. It is also associated with oxidative stress due to an imbalance between reactive oxygen species (ROS) and antioxidant defences. Unfortunately, long-term treatment with anti-epileptic drugs (AEDs) may produce hepatotoxicity, nephrotoxicity, and haematological alterations. In this way, some secondary metabolites of plants have been used to ameliorate the deterioration of nervous system disorders through their antioxidant properties, in addition to their anticonvulsant effects. An example is Centella asiatica, a plant noted to have a reputed neuroprotective effect related to its antioxidant activity. However, similar to conventional drugs, natural molecules may produce side effects when consumed in high doses, which could occur with Centella asiatica. Therefore, we aimed to evaluate the effect of a standardized extract of Centella asiatica L. Urb with tested anticonvulsant activity on biochemical and haematological parameters in rats subjected to lithium/pilocarpine-induced seizures. METHODS: Twenty-eight adult male Wistar rats were randomly divided into four groups (n = 7 each): vehicle (purified water), Centella asiatica (200 and 400 mg/kg), and carbamazepine (CBZ) (300 mg/kg) as a pharmacological control of anticonvulsant activity. Treatments were administered orally every 24 h for 35 consecutive days. On Day 36, SE was induced using the lithium/pilocarpine model (3 mEq/kg, i.p. and 30 mg/kg s.c., respectively), and the behavioural and biochemical effects were evaluated. RESULTS: Centella asiatica 400 mg/kg increased the latency to the first generalized seizure and SE onset and significantly reduced the time to the first generalized seizure compared to values in the vehicle group. Biochemical parameters, i.e., haematic cytometry, blood chemistry, and liver function tests, showed no significant differences among the different treatments. CONCLUSION: The dose of Centella asiatica that produces anticonvulsant activity in the lithium/pilocarpine model devoid of hepatotoxicity, nephrotoxicity, and alterations in haematological parameters suggests that the standardized extract of this plant could be of utility in the development of new safe therapies for the treatment of convulsions associated with epilepsy.

Optimizing rat and human blood cells sampling for in silico morphometric analysis.

Measurements of Morphometric Parameters of the Blood Cells (MPBC) are key for the diagnosis of both mental and metabolic diseases. Several manual approaches or computational methodologies are useful to provide reliable clinical diagnosis. The sample processing and data analysis is relevant, however the sample handling on the pre-analytical phase remains scarcely evaluated. The main goal of this study was to favor the preservation of blood smear using a histological resin. This strategy lead us two practical approaches, give a detailed morphometric description of white blood cells and establish reference intervals in male Wistar rats, which are scarcely reported. Blood smears from male Wistar rats (n = 120) and adult men were collected at room temperature. The integrity of Wright-stained cells was evaluated by an in silico image analysis from rat and human blood smear preserved with a toluene-based synthetic resin mounting medium. A single sample of human blood was used as a control of procedure. The reference intervals was established by cell counting. Based on the results of segmentation algorithm followed by an automatic thresholding analysis, the incorporation of resin favor the conservation of cell blood populations, and lead to identify morphologic features such as nucleus/cytoplasmic shape, granules presence and DNA appearance in nucleus of white blood cells. The use of a histological resin could favor a fast and efficient sample handling in silico MPBC measurements both in the species studied as in wild animals.

Anticonvulsant Effect of Turmeric and Resveratrol in Lithium/Pilocarpine-Induced Status Epilepticus in Wistar Rats.

Epilepsy is a chronic neurological disorder that lacks a cure. The use of plant-derived antioxidant molecules such as those contained in turmeric powder and resveratrol may produce short-term anticonvulsant effects. A total of 42 three-month-old male Wistar rats were divided into six groups (n = 7 in each group): Vehicle (purified water), turmeric (150 and 300 mg/kg, respectively), and resveratrol (30 and 60 mg/kg, respectively), administered per os (p.o.) every 24 h for 35 days. Carbamazepine (300 mg/kg/5 days) was used as a pharmacological control for anticonvulsant activity. At the end of the treatment, status epilepticus was induced using the lithium-pilocarpine model [3 mEq/kg, intraperitoneally (i.p.) and 30 mg/kg subcutaneously (s.c.), respectively]. Seizures were evaluated using the Racine scale. The 300 mg/kg of turmeric and 60 mg/kg of resveratrol groups had an increased latency to the first generalized seizure. The groups treated with 150 and 300 mg/kg of turmeric and 60 mg/kg of resveratrol also had an increased latency to status epilepticus and a decreased number of generalized seizures compared to the vehicle group. The chronic administration of turmeric and resveratrol exerts anticonvulsant effects without producing kidney or liver damage. This suggests that both of these natural products of plant origin could work as adjuvants in the treatment of epilepsy.