Pharmacological potential of tocopherol and doxycycline against traumatic brain injury-induced cognitive/motor impairment in rats

Rana, Arti; Singh, Shamsher; Deshmukh, Rahul; Kumar, Anoop

doi:10.1080/02699052.2020.1772508

Cited by 26 publications

(32 citation statements)

References 37 publications

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“…Levels of IL-6, IL-8 and TNFα were reduced in doxycycline-treated COPD patients. Moreover, doxycycline reduced neuroinflammation and preserved oxidative balance in traumatic brain injury-induced cognitive/motor impairments in rats due to its anti-inflammatory and free scavenging mechanisms [58]. Doxycycline could be a potential partner of COVID-19 therapies due to its anti-inflammatory effects.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2

et al. 2020

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In December 2019, a new severe acute respiratory syndrome coronavirus (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. Despite containment measures, SARS-CoV-2 spread in Asia, Southern Europe, then in America and currently in Africa. Identifying effective antiviral drugs is urgently needed. An efficient approach to drug discovery is to evaluate whether existing approved drugs can be efficient against SARS-CoV-2. Doxycycline, which is a second-generation tetracycline with broad-spectrum antimicrobial, antimalarial and anti-inflammatory activities, showed in vitro activity on Vero E6 cells infected with a clinically isolated SARS-CoV-2 strain (IHUMI-3) with median effective concentration (EC50) of 4.5 ± 2.9 µM, compatible with oral uptake and intravenous administrations. Doxycycline interacted both on SARS-CoV-2 entry and in replication after virus entry. Besides its in vitro antiviral activity against SARS-CoV-2, doxycycline has anti-inflammatory effects by decreasing the expression of various pro-inflammatory cytokines and could prevent co-infections and superinfections due to broad-spectrum antimicrobial activity. Therefore, doxycycline could be a potential partner of COVID-19 therapies. However, these results must be taken with caution regarding the potential use in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results to actual clinical treatment in patients. In vivo evaluation in animal experimental models is required to confirm the antiviral effects of doxycycline on SARS-CoV-2 and more trials of high-risk patients with moderate to severe COVID-19 infections must be initiated.

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Section: Discussionmentioning

confidence: 99%

In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2

et al. 2020

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“…115 Doxycycline and tocopherol alone and in combination treatment in experimental TBI, has proved to reduced neuro-inflammatory markers (IL-6, IL-1β, and TNF-α). 116…”

Section: Discussionmentioning

confidence: 99%

“…115 Doxycycline and tocopherol alone and in combination treatment in experimental TBI, has proved to reduced neuro-inflammatory markers (IL-6, IL-1β, and TNF-α). 116 Thus, in general, injury enhances gliosis and cytokines levels. As discussed earlier, cytokines have both beneficial and harmful effects.…”

Section: Discussionmentioning

confidence: 99%

Interferon-Gamma and Interleukin-1Beta Enhance the Secretion of Brain-Derived Neurotrophic Factor and Promotes the Survival of Cortical Neurons in Brain Injury

2020

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Neuro-inflammation is associated with the production of cytokines, which influence neuronal and glial functions. Although the proinflammatory cytokines interferon-γ (IFN-γ) and interleukin-1Beta (IL-1β) are thought to be the major mediators of neuro-inflammation, their role in brain injury remains ill-defined. The objective of this study was to examine the effect of IFN-γ and IL-1β on survival of cortical neurons in stab wound injury in mice. A stab wound injury was made in the cortex of male BALB/c mice. Injured mice (I) were divide into IFN-γ and IL-1β treatment experiments. Mice in I + IFN-γ group were treated with IFN-γ (ip, 10 µg/kg/day) for 1, 3 and 7 days and mice in I + IL-1β group were treated with 5 IP injection of IL-1β (0.5 µg /12 h). Appropriate control mice were maintained for comparison. Immunostaining of frozen brain sections for astrocytes (GFAP), microglia (Iba-1) and Fluoro-Jade B staining for degenerating neurons were used. Western blotting and ELISA for brain-derived neurotrophic factor (BDNF) were done on the tissues isolated from the injured sites. Results showed a significant increase in the number of both astrocytes and microglia in I + IFN-γ and I + IL-1β groups. There were no significant changes in the number of astrocytes or microglia in noninjury groups (NI) treated with IFN-γ or IL-1β. The number of degenerating neurons significantly decreased in I + IFN-γ and I + IL-1β groups. GFAP and BDNF levels were significantly increased in I + IFN-γ and I + IL-1β groups. Interferon-γ and IL-1β induce astrogliosis, microgliosis, enhance the secretion of BDNF, one of the many neurotrophic factors after brain injury, and promote the survival of cortical neurons in stab wound brain injury.

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“…Currently, available therapeutic options provide only symptomatic relief and unable to halt the progression of secondary injury that occur following TBI. 2 Recent preclinical studies 10 , 16 , 27 showed doxycycline as a promising choice that ameliorates the secondary brain injury. Hence, this study was designed to clinically investigate the benefit of adjunctive doxycycline use in acute TBI.…”

Section: Discussionmentioning

confidence: 99%

The effect of doxycycline on neuron-specific enolase in patients with traumatic brain injury: a randomized controlled trial

Mansour

Shama

Werida

2021

Therapeutic Advances in Chronic Disease

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Objective: We aimed to examine the effect of doxycycline on serum levels of neuron-specific enolase (NSE), a marker of neuronal damage in traumatic brain injury (TBI) patients. Methods: Patients were randomly assigned into two groups ( n = 25 each) to receive either placebo or doxycycline (200 mg daily), with their standard management for 7 days. Results: NSE serum levels in the doxycycline and control groups on day 3 were 14.66 ± 1.78 versus 18.09 ± 4.38 ng/mL, respectively ( p = 0.008), and on day 7 were 12.3 ± 2.0 versus 16.43 ± 3.85 ng/mL, respectively ( p = 0.003). Glasgow Coma Scale (GCS) on day 7 was 11.90 ± 2.83 versus 9.65 ± 3.44 in the doxycycline and control groups, respectively ( p = 0.031). NSE serum levels and GCS scores were negatively correlated ( r = −0.569, p < 0.001). Conclusion: Adjunctive early use of doxycycline might be a novel option that halts the ongoing secondary brain injury in patients with moderate to severe TBI. Future larger clinical trials are warranted to confirm these findings.

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Pharmacological potential of tocopherol and doxycycline against traumatic brain injury-induced cognitive/motor impairment in rats

Cited by 26 publications

References 37 publications

In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2

In Vitro Antiviral Activity of Doxycycline against SARS-CoV-2

Interferon-Gamma and Interleukin-1Beta Enhance the Secretion of Brain-Derived Neurotrophic Factor and Promotes the Survival of Cortical Neurons in Brain Injury

The effect of doxycycline on neuron-specific enolase in patients with traumatic brain injury: a randomized controlled trial

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