SARS-CoV-2 induces mitochondrial dysfunction and cell death by oxidative stress/inflammation in leukocytes of COVID-19 patients.

The inflammation and activation of the immune system induced by SARS-CoV-2 are mediated by a pro-oxidant microenvironment that can induce cytotoxic effects that enhance tissue damage, favoring organic deterioration. We investigated whether the induction of oxidative stress and inflammation by COVID-19 infection could inhibit mitochondrial function and cause cellular damage in leukocytes. We evaluated levels of oxidative/inflammation markers and their correlation with mitochondrial function and leukocyte cell death in COVID-19 patients at two moments: viremia and severe sepsis with multi-organ failure. COVID-19 induces increased oxidative stress and inflammation markers that activate cellular damage processes. In the viremia stage, an increase in peroxide, nitric oxide, carbonylated proteins, and IL-6 was observed, which was correlated with a marked inhibition of mitochondrial function, decreased cell viability, early apoptosis, necrosis, and leukocytes-reactivity. The severe sepsis stage with multi-organ failure also showed a further increase in levels of peroxide, carbonylated proteins, and IL-6, with a slight decrease in nitric oxide. This oxidative process and inflammation were correlated with less inhibition of mitochondrial function, decreased cell viability and an increase in late apoptosis, and morphology changes evidencing damage in the leukocytes. SARS-CoV-2 induced damage promotes levels of oxidative stress and inflammation markers and mitochondrial dysfunction that potentiate morphological changes and cell death in leukocytes. These processes explain the rapid changes in the immune system, and that present an initial over-activation and early massive death due to SARS-CoV-2 infection, promoting endothelial-alveolar damage that would cause multi-organ failure, sustained by oxidative stress and inflammation.

Antioxidant effect of Spirulina (Arthrospira) maxima in a neurotoxic model caused by 6-OHDA in the rat striatum.

There is evidence to support that an impaired energy metabolism and the excessive generation of reactive oxygen species (ROS) contribute to brain injury in neurodegenerative disorders such as Parkinson's disease (PD), whereas diets enriched in foods with an antioxidant action may modulate its progression. Several studies have proved that the antioxidant components produced by Spirulina, a microscopic blue-green alga, might prevent cell death by decreasing free radicals, inhibiting lipoperoxidation and upregulating the antioxidant enzyme systems. In our study, we investigated the protective effect of the Spirulina maxima (S. maxima) against the 6-OHDA-caused toxicity in the rat striatum. The S. maxima (700 mg/kg/day, vo) was administered for 40 days before and 20 days after a single injection of 6-OHDA (16 µg/2 µL) into the dorsal striatum. At 20-day postsurgery, the brain was removed and the striatum was obtained to evaluate the indicators of toxicity, such as nitric oxide levels, ROS formation, lipoperoxidation, and mitochondrial activity. These variables were found significantly stimulated in 6-OHDA-treated rats and were accompanied by declines in dopamine levels and motor activity. In contrast, the animals that received the chronic treatment with S. maxima had a restored locomotor activity, which is associated with the decreased levels of nitric oxide, ROS, and lipoperoxidation in the striatum, although mitochondrial functions and dopamine levels remained preserved. These findings suggest that supplementation with antioxidant phytochemicals (such as contained in S. maxima) represents an effective neuroprotective strategy against 6-OHDA-caused neurotoxicity vía free radical production to preserve striatal dopaminergic neurotransmission in vivo.