The Tetracyclines

Cunha, Burke A.; Comer, Joyce B.; Jonas, Mark E.

doi:10.1016/s0025-7125(16)31461-4

Cited by 45 publications

(21 citation statements)

References 29 publications

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“…The total dose of 495 mg͞kg per rat is significantly higher than those used in previous studies (12)(13)(14)(15)(16)(17)42). This pharmacological design produces an effective plasma concentration immediately after the first dose, which was sustained by succeeding doses over 5 days, a critical period for apoptotic neuronal and glial death as well as microglial activation after SCI (35,36,43,44). We observed a dramatic increase in the level of cytosolic cytochrome c that peaked 4-8 h p.i., a period that offers a pragmatic therapeutic window ( Fig.…”

Section: Discussionmentioning

confidence: 97%

Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury

Teng

Choi

Onario

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

307

184

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We investigated whether permeability transition-mediated release of mitochondrial cytochrome c is a potential therapeutic target for treating acute spinal cord injury (SCI). Based on previous reports, minocycline, a second-generation tetracycline, exerts neuroprotection partially by inhibiting mitochondrial cytochrome c release and reactive microgliosis. We first evaluated cytochrome c release at the injury epicenter after a T10 contusive SCI in rats. Cytochrome c release peaked at Ϸ4 -8 h postinjury. A dose-response study generated a safe pharmacological regimen that enabled i.p. minocycline to significantly lower cytosolic cytochrome c at the epicenter 4 h after SCI. In the long-term study, i.p. minocycline (90 mg͞kg administered 1 h after SCI followed by 45 mg͞kg administered every 12 h for 5 days) markedly enhanced long-term hind limb locomotion relative to that of controls. Coordinated motor function and hind limb reflex recoveries also were improved significantly. Histopathology suggested that minocycline treatment alleviated later-phase tissue loss, with significant sparing of white matter and ventral horn motoneurons at levels adjacent to the epicenter. Furthermore, glial fibrillary acidic protein and 2 ,3 cyclic nucleotide 3 phosphodiesterase immunocytochemistry showed an evident reduction in astrogliosis and enhanced survival of oligodendrocytes. Therefore, release of mitochondrial cytochrome c is an important secondary injury mechanism in SCI. Drugs with multifaceted effects in antagonizing this process and microgliosis may protect a proportion of spinal cord tissue that is clinically significant for functional recovery. Minocycline, with its proven clinical safety, capability to cross the blood-brain barrier, and demonstrated efficacy during a clinically relevant therapeutic window, may become an effective therapy for acute SCI.

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Section: Discussionmentioning

confidence: 97%

Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury

Teng

Choi

Onario

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

307

184

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“…To produce a motor function improving activity and neuroprotection, an adequate brain level should be achieved. This may be responsible for the observation that only the neuroprotection provided by minocycline was statistically significant, because although both drugs are lipophilic and pass the blood-brain barrier, minocycline could penetrate blood-brain barrier better than doxycycline due to its lower molecular weight and higher lipid solubility (Cunha et al, 1982;Kapusnik-Uner et al, 1996). Moreover the insufficient brain level could lead to contradictory studies reporting inactivity of minocycline and doxycycline in a model of Huntington's disease (Smith et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Effects of second generation tetracyclines on penicillin-epilepsy-induced hippocampal neuronal loss and motor incoordination in rats

et al. 2006

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“…Both antibiotics were used at dosages that produced concentrations similar to those achieved in humans after an oral dose of 100 mg of doxycycline and 500 mg of azithromycin, respectively (1,8,11,37). Doxycycline concentrations in serum samples and lung tissues were above the MICs for the test strains for about 18 h. In contrast, azithromycin concentrations in pulmonary tissues were 90 times greater than those in serum samples and persisted above the MICs for the test strains for 48 to 72 h after injection.…”

Section: Discussionmentioning

confidence: 99%

“…with a single dose of either doxycycline hyclate (10 mg/kg of body weight) or with azithromycin dihydrate (10 mg/kg of body weight). Groups of three to five animals were sacrificed 3,8,18, and 24 h after injection of doxycycline and 2, 6, 12, 24, 48, and 72 h after injection of azithromycin. At each time point, animals were killed by axillary bleeding, serum samples were collected, and lungs were removed in toto and frozen at Ϫ70ЊC.…”

mentioning

confidence: 99%

Effects of two antibiotic regimens on course and persistence of experimental Chlamydia pneumoniae TWAR pneumonitis

Malinverni

Kuo

Campbell

et al. 1995

Antimicrob Agents Chemother

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We studied the effects of two antibiotic regimens on the course of Chlamydia pneumoniae infection in the lungs of Swiss Webster mice. After intranasal challenge with isolates AR-388 (1.3 ؋ 10 7 inclusion-forming units per mouse) and AR-39 (1.5 ؋ 10 6 inclusion-forming units per mouse), groups of animals were treated with either doxycycline (10 mg/kg of body weight once a day for 3 days), azithromycin (10 mg/kg [single dose]), or saline. Responses were assessed by the isolation of organisms in cell culture, detection of TWAR DNA in lung tissues by PCR, and lung histology. Both regimens were effective in clearing infections induced by AR-388 (P ‫؍‬ 0.02 and 0.007 for doxycycline and azithromycin, respectively) compared with controls. TWAR DNA was detected in 77 and 25% of culture-negative lungs 2 weeks after treatment of AR-388 and AR-39 infections, respectively. Histological changes showed interstitial pneumonitis and were similar over time for all groups. Single-dose azithromycin produced drug levels in lung tissues above the MICs for the test strains for a period three times longer than that of single-dose doxycycline. We concluded that short-term antibiotic regimens were successful for the treatment of experimental TWAR pneumonitis in mice. TWAR DNA was frequently recovered from lung tissues after apparently successful treatment.

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The Tetracyclines

Cited by 45 publications

References 29 publications

Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury

Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury

Effects of second generation tetracyclines on penicillin-epilepsy-induced hippocampal neuronal loss and motor incoordination in rats

Effects of two antibiotic regimens on course and persistence of experimental Chlamydia pneumoniae TWAR pneumonitis

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