Histopathological alterations in mice under sub-acute treatment with Hintonia latiflora methanolic stem bark extract.

The indiscriminate use of herbal products is increasingly growing worldwide; nonetheless consumers are not warned about the potential health risks that these products may cause. Hintonia latiflora (Hl) is a tree native to the American continent belonging to the Rubiaceae family and its stem bark is empirically used mainly to treat diabetes and malaria; supplements containing Hl are sold in America and Europe without medical prescription, thus scientific information regarding its toxicity as a consequence of a regular consumption is needed. In the present study, the histopathological effect of 200 and 1000 mg/kg of HI methanolic stem bark extract (HlMeOHe) was evaluated in the small bowel, liver, pancreas, kidneys and brain of CD-1 male mice after oral sub-acute treatment for 28 days. No histopathological alterations were observed in the brain and small bowel of the treated animals; however, mice presented diarrhea from day 2 of treatment with both doses. No histological changes were observed in the tissues collected from the animals treated with 200 mg/kg, except for the liver that depicted periportal hepatitis. Animals treated with the higher dose showed in the liver sections hydropic degeneration, hepatitis and necrosis, kidney sections depicted tubular necrosis and in pancreas sections, hydropic degeneration of the pancreatic islets was observed. In conclusion, HlMeOHe damaged the liver with an oral dose of 200 mg/kg, and at 1000 mg/kg injured the kidneys and pancreas of the CD-1 male mice.

Ependymal damage in a Plasmodium yoelii yoelii lethal murine malaria model.

Malaria continues to be a major global health problem, and over 40% of the world's population is at risk. Severe or complicated malaria is defined by clinical or laboratory evidence of vital organ dysfunction, including dysfunction of the central nervous system (CNS). The pathogenesis of complicated malaria has not been completely elucidated; however, the development of the multiorgan affection seems to play an important role in the disruption of the blood brain barrier (BBB) that protects the CNS against chemical insults. Historically, the BBB has received more attention in the pathogenesis of malaria than have the cerebrospinal fluid-brain barrier (CSFBB) and ependymal cells. This perspective may be misguided because, in the context of disease or toxicity, the CSFBB is more vulnerable to many foreign invaders than are the capillaries. Given the lack on studies of the damage to the CSFBB and ependymal epithelium in experimental murine malaria, the present study evaluated morphological changes in the ependymal cells of CD-1 male mice infected with lethal Plasmodium yoelii yoelii (Pyy) via histopathology and scanning electron microscopy (SEM). Samples were taken two, four and six days post-infection (PI). No lesions were observed upon the initial infection. By the fourth day PI, fourth ventricle ependymal samples exhibited disruptions and roughened epithelia. More severe injuries were observed at six days PI and included thickened cilia and deep separations between the ependymal intercellular spaces. In some of the analyzed areas, the absence of microvilli and cell layer detachment were observed, and some areas exhibited blebbing surfaces. The ependymal cell lesions observed in the CD1 male mice infected with lethal Pyy seemed to facilitate the paracellular permeability of the CSFBB and consequently promote the access of inflammatory mediators and toxic molecules through the barrier, which resulted in damage to the brain tissue. Understanding the mechanism of ependymal disruption during lethal murine malaria could help to elucidate the local and systemic factors that are involved in the pathogenesis of the disease and may provide essential clues for the prevention and treatment of complicated human malaria.